RARE DISEASE
Rare carcinoma of stomach
Rare carcinoma of stomach
Rare carcinoma of stomach
Synonyms: Rare gastric carcinoma
Synonyms: Rare gastric carcinoma
Synonyms: Rare gastric carcinoma
Drug discovery
16
drugs
With orphan designations
Overview
Rare gastric carcinomas, including sarcomatoid carcinoma, squamous cell carcinoma (GSCC), and small cell carcinoma, represent <1% of gastric malignancies [1][5][9]. These tumors exhibit aggressive behavior, rapid progression, and poor prognosis due to limited response to conventional therapies. Diagnosis requires histopathological confirmation of distinct features (e.g., keratin pearls in GSCC, biphasic sarcomatoid morphology) [1][9][13].
Burden
Mortality: 5-year survival for GSCC is ~30–50%, inferior to gastric adenocarcinoma [9][17].
Clinical Challenges: Delayed diagnosis due to nonspecific symptoms (e.g., weight loss, bleeding); lack of guidelines for rare subtypes [1][5][16].
Economic Impact: High treatment costs from surgical complications and frequent recurrence [1][12].
Therapies
Surgery: Primary approach (e.g., D2 gastrectomy), though recurrence rates remain high post-resection [1][3][11].
Chemotherapy: Limited evidence for perioperative/adjuvant use; cisplatin-based regimens often used empirically [5][9].
Immunotherapy: PD-1/PD-L1 inhibitors (e.g., nivolumab) under investigation but not standardized [7].
Categories: rare gastroenterological diseases, rare neoplastic diseases
Research Papers
417 drug discovery papers about Rare carcinoma of stomach, with 2 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
417 drug discovery papers about Rare carcinoma of stomach, with 2 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-25 | Case Report: Conversion therapy with chemotherapy, antiangiogenic therapy, and immunotherapy for locally advanced synchronous gastric hepatoid adenocarcinoma and poorly differentiated adenocarcinoma
Hepatoid adenocarcinoma of the stomach (HAS) is a rare, aggressive gastric carcinoma that is frequently associated with elevated alpha-fetoprotein (AFP). We report a patient with resolved hepatitis B virus infection and two spatially distinct gastric lesions: poorly differentiated adenocarcinoma in the gastric body and HAS in the gastric angularis. The disease was initially considered unresectable. After multidisciplinary evaluation, the patient received oxaliplatin, S-1, sintilimab, and apatinib. Treatment produced radiological regression and AFP normalization, enabling total gastrectomy. Histopathology showed no viable carcinoma in either tumor bed or in 20 regional lymph nodes, confirming a pathological complete response. This case illustrates the potential role of individualized conversion therapy in selected patients with alpha-fetoprotein-producing gastric cancer. It does not establish the four-agent regimen as standard care. Interpretation is limited by the single-patient design, short follow-up, absence of lesion-specific sequencing and serial hepatitis B virus DNA data, and a nonstandardized maintenance strategy.
2026-09-18 | Rapidly Progressive Gastric Poorly Differentiated Neuroendocrine Carcinoma Mimicking Gastrointestinal Stromal Tumor: A Case Report.
Poorly differentiated gastric neuroendocrine carcinoma (NEC) represents a rare but highly aggressive malignancy, typically diagnosed at advanced stages, which are associated with poor prognosis. We present a case of a 71-year-old male with a history of distal gastrectomy who developed recurrent gastrointestinal bleeding from a subepithelial gastric mass. The lesion initially measured approximately 2 cm and demonstrated endoscopic and radiological features reminiscent of gastrointestinal stromal tumors (GIST). Repeated endoscopic biopsies indicated weak c-KIT and DOG1 positivity; however, the mass enlarged rapidly to 8 cm within 2 months, accompanied by multiple hepatic metastases. Ultrasound-guided liver biopsy confirmed the diagnosis of poorly differentiated gastric NEC. Cisplatin-based palliative chemotherapy was initiated, but the patient died within 3 weeks due to persistent hemorrhage and rapid clinical decline. Although uncommon, gastric NEC may closely mimic GIST both clinically and pathologically. Accurate differentiation between these entities is essential, given their markedly divergent prognoses and therapeutic approaches.
2026-08-10 | An example of successful combination treatment of a patient with primary multiple synchronous squamous cell carcinoma of the esophagus and squamous cell carcinoma of the stomach
Our work presents an extremely rare case of primary synchronous tumors in the esophagus and stomach with a similar histological type, with a different approach to treatment in a young patient. The high sensitivity of squamous cell carcinoma to drug therapy was vividly reflected in our example and clinically proven in the form of complete tumor resorption in the esophagus. Despite the generally accepted standards of treatment, we were dictated an individual treatment plan, thanks to which we managed to limit ourselves to gastric surgery, thereby avoiding the extended resection stage on the esophagus, thereby maintaining an optimal quality of life.
2026-08-07 | Postoperative Adjuvant Treatment Decision for Early Epstein-Barr Virus-Associated Gastric Cancer.
Epstein-Barr virus-associated gastric cancer (EBVaGC) is a relatively rare clinical subtype. Despite its generally favorable prognosis, preoperative diagnosis remains challenging, and no established consensus exists regarding postoperative adjuvant treatment strategies for early-stage patients with high-risk pathological factors. This study reports a female case of early-stage EBVaGC of the lymphoepithelioma-like carcinoma subtype complicated with perineural invasion (a high-risk factor), and systematically explores the etiology, pathological features, key diagnostic points, individualized adjuvant therapy options, and prognosis of EBVaGC. The aim is to improve clinicians' understanding of this gastric cancer subtype, reduce its misdiagnosis rate, and accelerate the development of standardized diagnostic and treatment pathways. A case of a 60-year-old female patient admitted with "abdominal pain and distension for more than 1 year" was reported, and postoperative pathology confirmed EBVaGC. The clinical manifestations and diagnostic and treatment process were analyzed in combination with a review of relevant literature from recent years. Preoperative gastroscopic biopsy revealed poorly differentiated adenocarcinoma of the gastric mucosa. The patient underwent laparoscopic radical subtotal gastrectomy with lymph node dissection. Postoperative pathology confirmed EBVaGC. After symptomatic treatment, the patient improved and was discharged from the hospital. One month after surgery, no disease progression was observed and the SOX regimen was administered. The patient tolerated the treatment well, and the next cycle of chemotherapy is currently planned. EBVaGC lacks specific clinical manifestations, and laboratory findings may be within normal ranges at the time of onset. Reliance solely on conventional gastroscopy and histopathological biopsy can easily lead to misdiagnosis and inappropriate treatment. Epstein-Barr virus-encoded RNA in situ hybridization is the core diagnostic modality for definitive diagnosis. This subtype generally has a favorable prognosis. However, for patients with high-risk pathological factors such as perineural invasion and tumor invasion into the muscularis propria, standardized postoperative individualized adjuvant therapy should be administered based on tumor stage and molecular profiles.
2026-08-07 | Capmatinib for High-Level MET-Amplified Metastatic Gastric Cancer Identified by Comprehensive Genomic Profiling: A Case Report and Literature Review.
High-level MET gene amplification is a rare but potentially actionable alteration in gastric cancer. Previous phase III trials of MET-targeted therapies enrolled broadly MET-positive populations without prospective selection for high-level MET amplification, and no MET-directed therapy is currently established for this disease. Here, we report a 74-year-old woman with heavily pretreated metastatic gastric adenocarcinoma harboring high-level MET amplification (copy number 21) identified by comprehensive genomic profiling. Following expert panel review, the patient received capmatinib through the BELIEVE trial (NCCH1901; jRCTs031190104) and achieved a confirmed partial response at 8 weeks, with a 43.7% reduction in the sum of target lesion diameters. The response was maintained at 16 weeks; disease progression was observed at 24 weeks, with a progression-free survival of approximately 5.5 months. In the context of a literature review of MET-targeted therapies in gastric cancer, this case supports further investigation of selective MET inhibition in gastric cancer with high-level MET amplification, a rare molecular subset not prospectively enriched in previous clinical trials.
proteins
2025-10-13 | Personalized peptide vaccines induce predicted T cell responses against signet ring cell carcinoma—a case report
T cell-based immunotherapies increasingly include personalized neoantigen vaccines that target tumor-specific mutations. However, despite their promise, current neoantigen vaccines show limited and unpredictable clinical benefit, with T cell responses observed in only a subset of patients. To overcome these limitations, we developed the VERDI (Vaccine Epitopes Ranked by Digital Intelligence) System—a cloud-based computational platform that integrates a patient’s human leukocyte antigen (HLA) class I and II genotype with selected tumor-associated antigens (TAAs), including cancer-testis antigens (CTAs), to identify peptides with high predicted immunogenicity and low risk of immune-related adverse events (irAEs). Using the VERDI System, we designed ten personalized peptide vaccines for a patient with metastatic signet ring cell carcinoma (SRCC), a rare and aggressive gastric cancer with limited treatment options. All ten VERDI vaccines were well tolerated and consistently induced tumor-specific T cell responses following a single administration, without the need for checkpoint inhibitors. The patient survived for 15 months—substantially longer than the reported median survival of 5.6 months in metastatic SRCC—highlighting the potential of this individualized, predictive vaccine platform to improve outcomes in advanced cancer.
2025-06-12 | Last decade of advances in gastric neuroendocrine tumors: Innovations, challenges, and future directions.
Gastric neuroendocrine tumors (G-NETs) are rare tumors originating from enterochromaffin-like cells, with an incidence of 0.4 per 100000 annually. There are three main types: (1) Type I, linked to chronic atrophic gastritis and hypergastrinemia, makes up 75%-80% of G-NETs; (2) Type II, associated with Zollinger-Ellison syndrome (ZES) and multiple endocrine neoplasia, comprises 5%; and (3) Type III, sporadic tumors with a higher metastatic potential, accounting for 15%-25%. Diagnosis involves endoscopy, biopsy, and histological examination. Additional methods include serum gastrin testing, immunohistochemistry, and imaging techniques such as computer tomography or magnetic resonance imaging for detecting metastasis. Type I treatment usually involves endoscopic resection (ER), with surgical resection for recurrence. Somatostatin analogs (SSAs) can reduce tumor size, and the prognosis is generally excellent. Type II treatment centers on surgical removal of the gastrinoma, with ER for smaller lesions and SSAs for symptom management. Type III requires surgical resection (partial or total gastrectomy) with lymph node dissection, and possibly chemotherapy. This type has a worse prognosis due to its aggressive nature. Emerging treatments like Peptide Receptor Radionuclide Therapy are promising for advanced cases, and ongoing research into immunotherapies is expanding future treatment options. Regular endoscopic follow-up is crucial to monitor for recurrence or metastasis across all types. Our literature review explores the current perspectives on G-NETs and highlights the importance of further research to improve diagnostic precision and treatment, particularly for those associated with less favorable cases. To improve diagnostic precision and treatment, particularly for those associated with less favorable cases. A systematic search was conducted in PubMed, Scopus, and Web of Science until September 2024. Two independent reviewers screened titles, abstracts, and full texts for eligibility based on G-NET treatment in adults. Eligible studies included cohort studies, clinical trials, case series, and case reports, while in vitro, pediatric, and non-English studies were excluded. Relevant data were extracted independently, and disagreements were resolved through discussion. Study quality was assessed using appropriate tools. G-NETs are rare, classified into three types: (1) Type I; (2) Type II; and (3) Type III. Type I G-NETs, often associated with chronic atrophic gastritis, are typically slow-growing and low-grade, with favorable outcomes following surgical resection. Type II G-NETs arise in hypergastrinemia conditions like multiple endocrine neoplasia and ZES, showing moderate malignancy risk. Type III G-NETs, the most aggressive and least common, present with distant metastases and poor prognosis. Diagnosis relies on endoscopy, imaging, and biomarkers like chromogranin A. Treatment varies by type, ranging from ER to aggressive surgery and chemotherapy for advanced cases. Regular follow-up is essential to monitor recurrence, particularly for type III G-NETs. G-NETs require tailored diagnosis and treatment based on type and stage. Types I and II generally have better prognosis, while types III and IV are linked to poorer outcomes due to invasion and metastasis. Treatment strategies vary from ER for type I to extensive surgery for type III. Emerging therapies, like somatostatin analogs and peptide-receptor radionuclide therapies, show promise in advanced cases. Further research is essential to improve early diagnosis and treatment, particularly for high-risk lesions.
2023-08-04 | The epigenetic modifier lysine methyltransferase 2C is frequently mutated in gastric remnant carcinoma.
Gastric remnant carcinoma (GRC), which occurs in the stomach after partial gastrectomy, is a rare and aggressive form of gastric adenocarcinoma (GAC). Comprehensive profiling of genomic mutations in GRC could provide the basis for elucidating the origin and characteristics of this cancer. Herein, whole-exome sequencing (WES) was performed on 36 matched tumor-normal samples from patients with GRC and identified recurrent mutations in epigenetic modifiers, notably KMT2C, ARID1A, NSD1, and KMT2D, in 61.11% of cases. Mutational signature analysis revealed a low frequency of microsatellite instability (MSI) in GRC, which was further identified by MSIsensor, MSI-polymerase chain reaction, and immunohistochemistry analysis. Comparative analysis demonstrated that GRC had a distinct mutation spectrum compared to that of GAC in The Cancer Genome Atlas samples, with a significantly higher mutation rate of KMT2C. Targeted deep sequencing (Target-seq) of an additional 25 paired tumor-normal samples verified the high mutation frequency (48%) of KMT2C in GRC. KMT2C mutations correlated with poor overall survival in both WES and Target-seq cohorts and were independent prognosticators in GRC. In addition, KMT2C mutations were positively correlated with favorable outcomes in immune checkpoint inhibitor-treated pan-cancer patients and associated with higher intratumoral CD3+ , CD8+ tumor-infiltrating lymphocyte counts, and PD-L1 expression in GRC samples (p = 0.018, 0.092, 0.047, 0.010, and 0.034, respectively). Our dataset provides a platform for information and knowledge mining of the genomic characteristics of GRC and helps to frame new therapeutic approaches for this disease.
2019-11-19 | KMT2C Mutations in Diffuse-Type Gastric Adenocarcinoma Promote Epithelial-to-Mesenchymal Transition.
Lauren diffuse-type gastric adenocarcinomas (DGAs) are generally genomically stable. We identified lysine (K)-specific methyltransferase 2C (KMT2C) as a frequently mutated gene and examined its role in DGA progression. We performed whole exome sequencing on tumor samples of 27 patients with DGA who underwent gastrectomy. Lysine (K)-specific methyltransferase 2C (KMT2C) was analyzed in DGA cell lines and in patient tumors. KMT2C was the most frequently mutated gene (11 of 27 tumors [41%]). KMT2C expression by immunohistochemistry in tumors from 135 patients with DGA undergoing gastrectomy inversely correlated with more advanced tumor stage (P = 0.023) and worse overall survival (P = 0.017). KMT2C shRNA knockdown in non-transformed HFE-145 gastric epithelial cells promoted epithelial-to-mesenchymal transition (EMT) as demonstrated by increased expression of EMT-related proteins N-cadherin and Slug. Migration and invasion in gastric epithelial cells following KMT2C knockdown increased by 47- to 88-fold. In the DGA cell lines MKN-45 and SNU-668, which have lost KMT2C expression, KMT2C re-expression decreased expression of EMT-related proteins, reduced cell migration by 52% to 60%, and reduced cell invasion by 50% to 74%. Flank xenografts derived from KMT2C-expressing DGA organoids, compared with wild-type organoids, grew more slowly and lost their infiltrative leading edge. EMT can lead to the acquisition of cancer stem cell (CSC) phenotypes. KMT2C re-expression in DGA cell lines reduced spheroid formation by 77% to 78% and reversed CSC resistance to chemotherapy via promotion of DNA damage and apoptosis. KMT2C is frequently mutated in certain populations with DGA. KMT2C loss in DGA promotes EMT and is associated with worse overall survival.
2012-02-13 | Spontaneous complete regression of gastric large-cell neuroendocrine carcinoma: mediated by cytomegalovirus-induced cross-autoimmunity?
Spontaneous regression of malignant tumour is a rare phenomenon. This report describes such an occurrence in a gastric large cell neuroendocrine carcinoma of a 77-year-old man. The patient presented with dyspepsia, and biopsy of the fungating mass in the cardia showed a high grade neuroendocrine carcinoma. The pre-operative biopsy taken after 3 months showed chronic inflammation and cytomegalovirus inclusions, but no tumour. In the gastrectomy specimen, no residual tumour was found. Instead, there were foamy histiocytes, chronic inflammatory cells and fibrovascular tissue splitting apart the muscularis propria. In addition, there was ganglionitis involving the myenteric plexus, even in areas of the stomach away from the inflamed site. Chemotherapy, radiotherapy or alternative medicine (including herbal medicine) had not been given. We postulate that cytomegalovirus infection initiated a cross-autoimmune reaction against neuronal cells, and this reaction "unintentionally" eliminated the carcinoma cells which also expressed neural antigens.
cell therapies
2026-09-06 | Gastric perforation repaired by hepatic round ligament: Case report and literature review.
Gastric perforation is a rare but life-threatening complication of gastric cancer, often presenting with acute peritonitis and requiring emergent surgical repair. The conventional treatment relies on an omental patch (Graham's technique); however, this approach is not always feasible, particularly in patients with advanced disease or omental involvement. We report the case of a 44-year-old male with advanced gastric adenocarcinoma complicated by peritoneal carcinomatosis who presented with acute abdomen following stent insertion. Imaging confirmed gastric perforation and generalized peritonitis. During emergent laparoscopic exploration, the omentum was unsuitable due to carcinomatous infiltration. Instead, the hepatic round ligament was mobilized and used as a patch to seal the perforation, achieving effective closure. The patient initially recovered well postoperatively; however, he later deteriorated due to progression of his underlying malignancy and died on postoperative day 16. This case highlights the hepatic round ligament as a viable alternative to the omentum in repairing gastric perforations, particularly in malignant or hostile abdominal environments. Wider application of this technique warrants further study to establish its safety and long-term outcomes.
2025-09-18 | Clinicopathological Features and Management of Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS).
Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare hereditary gastric cancer syndrome linked to APC promoter IB variants and characterized by gastric polyposis. Its natural history and management are poorly defined. We sought to characterize the clinicopathological features of GAPPS and infer management guidelines. We retrospectively analyzed individuals with GAPPS enrolled in a natural history study from January 2017 to September 2023. Demographics, pathogenic gene variants, endoscopic findings, and histopathology results were studied. Of 21 patients with GAPPS, 11 (52%) were male, and most were non-Hispanic white (71%). Median age at germline genetic testing was 44 years (range 12-75 years), and all individuals had a pathogenic variant in the APC promoter IB. Esophagogastroduodenoscopy (EGD) was performed in almost all patients (91%), with a median age of 37 years (range 12-75 years) at initial EGD. Gastric polyps carpeting the fundus and body with antral sparing were noted in all individuals. Gastric adenocarcinoma (n = 3), high-grade dysplasia (n = 7), low-grade dysplasia (n = 3), and benign fundic gland polyposis (n = 6) were demonstrated on endoscopic biopsies. Then, 43% (9/21) of patients underwent total gastrectomy (TG) at a median age of 44 years (range 15-63 years). Histopathology of final gastrectomy specimens demonstrated more advanced pathology compared with endoscopic biopsies in five of nine patients. Given the challenge of effective endoscopic surveillance owing to extensive polyposis, and the risk of malignant transformation, prophylactic TG should be considered for patients with GAPPS. Longitudinal studies are needed to delineate lifetime cancer risk and clinical management guidelines.
2023-07-31 | CD4-/CD8- double-negative tumor-infiltrating lymphocytes expanded from solid tumor tissue suppress the proliferation of tumor cells in an MHC-independent way.
Tumor-infiltrating lymphocytes (TILs) have shown remarkable clinical responses in some patients with advanced solid tumors. As a rare subset of TILs, CD4-/CD8- double-negative T cells (DNTs) were poorly known. This study aims to investigate the characteristics and function of CD3+CD4-CD8- TILs (double-negative TIL, DN-TILs) derived from solid tumor. DN-TILs were derived and expanded ex vivo from resected gastric carcinoma tissue and phenotyped by flow cytometry. The cytotoxicity of DN-TILs was determined against established tumor cell lines in vitro or through in vivo adoptive transfer into xenograft models. K562 cells were transferred with the HLA gene to verify whether the cytotoxicity of DN-TILs was MHC-independent. Flow cytometric analysis revealed a high-purity population of DN-TILs (> 97%) within CD3+ TILs, which expanded more than 800-folds in 2 weeks, consisting of a mixture of alpha-beta (αβ) and gamma-delta (γδ) T-cell receptor (TCR)-expressing cells (with the majority being αβ-TCR, > 95%). Using single-cell RNA sequencing, the expanded DN-TILs were categorized into four main subsets, Natural Killer T cells (approximately 80%, 5563 in 7028), Progenitor cells, Germ cells and T helper2 cells. DN-TILs exhibited a broad anticancer cytotoxicity in a donor-unrestricted manner against various cancer cell lines derived from pancreatic cancer (Panc-1), gastric cancer (HGC-27), ovarian cancer (SKOV-3), malignant melanoma (A375). The cytotoxicity was MHC-independent, which was not altered in K562 transferring with HLA gene or not. DN-TILs significantly reduced tumor volume in xenograft models with superior tumor-homing ability and low off-target toxicity. Gastric carcinoma derived DN-TIL can target tumor cells in vitro and in vivo. DN-TILs have the potential to be used as a adoptive cell therapy for solid cancers with both the advantages of DNT and TIL.
2022-12-02 | Therapeutic plasma exchange in gastric signet ring cell carcinoma presenting as microangiopathic hemolytic anemia: A rare case report.
Microangiopathic hemolytic anemia (MAHA) defines a group of disorders characterized by the formation of microthrombi in capillaries and arterioles and the fragmentation of erythrocytes that pass through. Cancer-related MAHA is a rare but serious condition that is encountered in patients diagnosed with a malignancy. This clinical picture is thought to be linked to certain tumor characteristics; particularly, adenocarcinoma histology, vascular invasion, and bone marrow infiltration. MAHA is most commonly associated with tumors of gastric, prostate, and breast origin. The optimal treatment is not clear; however, there is evidence for the importance of promptly starting an effective antineoplastic regimen and it was also reported that administering therapeutic plasma exchange (TPE) therapy for immunocomplex removal could be beneficial for patients with symptoms of bleeding and thrombosis. Here, we present a case that presented a picture of MAHA secondary to gastric signet-ring cell adenocarcinoma (SRCC). The clinical picture was initially evaluated as thrombotic thrombocytopenic purpura and the patient benefited significantly from the TPE treatment administered before the adenocarcinoma diagnosis was confirmed. In this period, epistaxis stopped, platelet count increased from 25 × 109 /L to 162 × 109 /L, fragmented erythrocyte rate in the peripheral smear decreased by more than 75% and other laboratory findings of hemolysis (LDH, bilirubin, etc.) significantly improved.
2022-03-08 | Filling in the "GAPPS": an unusual presentation of a child with gastric adenocarcinoma and proximal polyposis of the stomach.
Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a very rare gastric polyposis syndrome characterized by numerous polyps of the gastric fundus and body. We present the unusual case of a 10-year-old Polish-American male with history of eosinophilic esophagitis, who was found to have multiple fundic gland polyps (FGP) with low grade dysplasia on esophagogastroduodenoscopy. Subsequent evaluation including genetic testing confirmed the diagnosis of GAPPS, and after exhaustive multidisciplinary consultation the decision was made to proceed with prophylactic total gastrectomy given the markedly increased risk of gastric adenocarcinoma in GAPPS patients. To our knowledge, this represents the youngest patient diagnosed with GAPPS and the youngest patient who has undergone prophylactic gastrectomy for this disease at age 8 and 10 years, respectively. The pathophysiology, presentation, and treatment of GAPPS in a pediatric patient are discussed.
antibodies
2026-09-23 | Successful non-surgical management of locally advanced gastric adenocarcinoma with squamous differentiation and programmed death-ligand 1 combined positive score 75: a case report.
Poorly differentiated gastric adenocarcinoma with squamous differentiation is a rare and aggressive malignancy, with limited representation in the literature. Its biological behaviour remains poorly characterized, and prognosis is generally poor. Here, we present a case that highlights the role of biomarker-driven, non-surgical management in advanced gastric malignancy, particularly in the context of high PD-L1 expression in an elderly patient. A 75-year-old Syrian Arab male presented with anaemia, weight loss and anorexia. Imaging revealed a large ulcerated gastric mass measuring 9 × 11 cm with perigastric lymphadenopathy and local invasion, but no evidence of distant metastasis. Histopathological examination confirmed poorly differentiated adenocarcinoma with squamous differentiation. Immunohistochemistry demonstrated diffuse p40 positivity and focal cytokeratin 7 (CK7) positivity. Notably, programmed death-ligand 1 (PD-L1) expression was strongly positive, with a combined positive score (CPS) of 75. The patient was started on combined chemotherapy (oxaliplatin and 5-fluorouracil) and immunotherapy (nivolumab). Remarkably, follow-up positron emission tomography-computed tomography (PET-CT) at 3 months showed a reduction in tumour size and metabolic activity, with near complete radiological remission by 6 months. At 1-year follow-up, the patient remains clinically well and disease-free without surgical intervention. This case illustrates how high PD-L1 expression may substantially alter the expected clinical course of gastric cancer, even in rare and poorly differentiated subtypes typically associated with poor outcomes. The observed durable clinical complete response underscores the potential of biomarker-guided chemo-immunotherapy and supports consideration of non-surgical approaches in selected patients.
2026-08-13 | Case Report: Synchronous Esophageal Squamous Cell Carcinoma and Gastric Cardia Adenocarcinoma with Hepatoid Differentiation After Neoadjuvant Chemoimmunotherapy.
Background/Objectives: Hepatoid adenocarcinoma is a rare adenocarcinoma subtype. Synchronous esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma with hepatoid differentiation is exceptionally uncommon. This report describes lesion-specific staging, pathological response assessment, and individualized management after neoadjuvant chemoimmunotherapy. Methods: De-identified clinical, imaging, laboratory, operative, and pathological data were retrospectively reviewed. Both lesions were staged according to the AJCC 8th edition and reassessed using the CAP modified Ryan four-tier tumor regression grading system. Results: A 61-year-old man presenting with dysphagia had separate ESCC and gastric cardia adenocarcinoma, both staged cT2N0M0. One cycle of pembrolizumab 200 mg, nab-paclitaxel 300 mg, and cisplatin 100 mg was administered. Agranulocytosis precluded further neoadjuvant therapy; after neutrophil recovery, R0 resection was performed. Pathological review showed ESCC ypT1aN0M0, score 1, and cardia adenocarcinoma ypT1aN0M0, score 3, with approximately 30% regional hepatoid differentiation. All 10 examined lymph nodes were negative. AFP was not measured before treatment; post-treatment/preoperative values were 14.45 and 14.68 ng/mL, and the postoperative value was 6.08 ng/mL. Postoperative tislelizumab monotherapy was selected as an individualized, non-standard strategy, mainly because of affordability. At approximately 6 months after surgery, no recurrence, metastasis, or maintenance-related adverse event was identified. Conclusions: This case emphasizes biopsy under-sampling and lesion-specific staging and pathological assessment. The regression-score difference is descriptive and confounded by baseline burden, histology, and one-cycle exposure; the AFP findings do not validate a surveillance biomarker.
2026-07-03 | MET Expression in Upper Gastrointestinal Adenocarcinoma: Prevalence, Prognostic Impact, and Implications for Anti-MET Antibody-Drug Conjugate Therapy.
MET is an actionable receptor tyrosine kinase, and MET-directed antibody-drug conjugates (ADCs) have recently entered clinical practice with FDA approval in non-small cell lung cancer and are now being evaluated across gastrointestinal malignancies, with patient selection based on MET immunohistochemistry (IHC) 3+ membranous staining at varying percentage thresholds. However, robust real-world data on MET protein expression and clinically relevant ADC-aligned thresholds in upper GI adenocarcinomas remain limited. We profiled 1532 upper GI adenocarcinomas using the clinically validated VENTANA MET (SP44) IHC assay. MET was stratified by (i) 3+ membranous staining fractions (any, ≥ 10%, ≥ 50%) reflecting contemporary ADC eligibility concepts and (ii) H-score (0-300; high ≥ 150). Overall survival analyses and multivariable Cox regression analyses were performed. High MET expression was uncommon (H-score ≥ 150: 2.3%; any 3+: 1.6%; ≥ 10% 3+: 1.3%; ≥ 50% 3+: 1.0%) and enriched in advanced T stage. MET IHC strongly predicted MET amplification (H-score ≥ 150: 63.6% amplified vs. 2.4% in negatives; any 3+: 75.0% vs. 2.6%; all p < 0.001). Any MET 3+ staining was independently associated with inferior overall survival (adjusted HR 2.22, 95% CI 1.29-3.83). Most MET 3+ tumors lacked concurrent HER2 positivity, Claudin-18.2 expression, or dMMR/MSI. In the largest real-world cohort to date, MET overexpression identifies a rare, biologically aggressive subset with poor outcomes. By applying the latest MET-ADC-relevant IHC criteria (including the ≥ 10% 3+ threshold), this study provides clinically translatable prevalence estimates and supports standardized MET testing to inform prospective MET-directed ADC trials in upper GI adenocarcinoma.
2026-05-28 | Multi-omics approaches to unveil the mixed molecular characteristics of hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation.
e16109 Background: Hepatoid adenocarcinoma of stomach with neuroendocrine differentiation (HAS-NEC) is an extremely rare subtype of gastric cancer, and there is currently no systematic research focused on this uncommon subtype. This study aims to investigate the clinicopathological and molecular characteristics of this rare subtype, thereby providing a reference for precision therapy for such patients. Methods: We retrospectively collected tumor tissue and adjacent carcinoma tissue samples from 84 patients, along with corresponding clinicopathological information, for whole exome sequencing and transcriptome sequencing. Spearman correlation analysis and unsupervised clustering analysis were employed to explore the molecular characteristics of HAS-NEC and to assess the similarities and differences among the various sample groups. Results: From the perspective of clinical pathological features, HAS-NEC exhibited greater similarity to HAS patients, with no significant differences in all clinicopathological characteristics. HAS-NEC patients possessed distinct genomic features compared to both HAS and NEC patients, with TTN being the most frequently mutated gene, occurring in 90% of cases. Mutations in TET1 were exclusive to HAS-NEC patients and were not detected in the other two groups. At the transcriptional level, HAS-NEC patients showed greater similarity to HAS patients, demonstrating more comparable transcriptional expression patterns. Lastly, we identified a potential therapeutic target, ZFHX4, whose mutations influence the transcriptional expression and prognosis of gastric cancer patients, further impacting immune infiltration and response to immunotherapy. Conclusions: Patients with HAS-NEC exhibited unique molecular biological characteristics that could not be simply viewed as a combination of HAS and NEC.
2026-02-23 | Long-term durable response to Sintilimab therapy in synchronous lung squamous cell carcinoma and gastric adenocarcinoma: a rare case report.
Gastric cancer (GC) and lung squamous cell carcinoma (SCC) are major global causes of cancer-related morbidity and mortality, but their synchronous occurrence is exceedingly rare and poses substantial diagnostic and therapeutic challenges. This report describes a 64-year-old male with synchronous lung SCC and gastric adenocarcinoma who achieved long-term disease control with Sintilimab monotherapy. Initial imaging and biopsy confirmed poorly differentiated lung SCC (PD-L1 CPS: 2), while PET-CT and endoscopy identified a gastric lesion later confirmed as adenocarcinoma (PD-L1 CPS: 5). Despite indications for chemotherapy, the patient declined cytotoxic therapy and initially refused surgery. He was treated with Sintilimab plus Anlotinib, resulting in lung lesion regression. Progression of gastric obstruction led to gastrectomy two years later; subsequent lung recurrence was managed surgically. Both tumors showed high proliferative indices (Ki-67 ~80-90%) and PD-L1 expression, supporting responsiveness to immune checkpoint blockade. This case highlights the feasibility of immune monotherapy in managing complex synchronous malignancies, especially when standard treatments are declined.
other
2025-09-09 | Pediatric Alpha-Fetoprotein-Producing Gastric Cancer Presenting With Dysphagia and Multiple Liver Tumors.
Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) is resistant to chemotherapy and is associated with poor prognosis. Pediatric gastric cancer has an incidence of 0.02% among gastric cancer patients, with a median survival of 5 months. A 13-year-old boy presented with progressive dysphagia for 2 months, accompanied by loss of appetite and significant weight loss. Liver dysfunction and multiple lesions were observed. Laboratory investigations revealed elevated liver enzymes and tumor markers, including AFP, at 24 502 ng/mL. Computed tomography (CT) showed thickening of the gastric cardia and multiple liver lesions. Upper gastrointestinal endoscopy revealed a type 2 tumor in the cardia. Histopathology confirmed adenocarcinoma, and immunohistochemical staining was positive for AFP, establishing a diagnosis of AFPGC with liver metastases (Stage IV). Given the unresectable and HER2-negative nature of the cancer, chemotherapy with TS-1 and cisplatin was initiated, resulting in a temporary reduction in AFP levels and tumor size. However, disease progression was noted after 3 months, requiring a switch in treatment to ramucirumab, paclitaxel, bleomycin, etoposide, cisplatin, or a study drug. Despite these efforts, the patient succumbed to the disease 16 months after initial treatment. AFPGC in children is extremely rare, with few reported cases. The 16-month survival observed in this case exceeds previously reported durations (8 and 4 months). Systematic evaluation of persistent gastrointestinal symptoms enabled earlier diagnosis. Standard adult gastric cancer treatment protocols appeared more effective than AFP-tumor-specific regimens, suggesting they may be optimal for pediatric AFPGC as well. Early diagnosis through detailed history-taking and prompt endoscopic examinations in children with gastrointestinal symptoms may lead to significantly prolonged survival and improved management in this rare malignancy.
2025-01-23 | Hepatoid adenocarcinoma of the stomach with ideal response to neoadjuvant chemo-immunotherapy: a case report.
Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer characterized by histological features resembling hepatocellular carcinoma. Surgical intervention remains the preferred treatment modality for eligible patients. However, the efficacy of neoadjuvant therapy and alternative treatment regimens has been found to be suboptimal. Consequently, due to the high metastatic potential and unfavorable biological behavior of HAS, the prognosis for affected patients is exceedingly poor. We present a case involving a 64-year-old male diagnosed with advanced HAS, who demonstrated significant antitumor responses following a preoperative regimen of chemotherapy combined with immunotherapy, specifically utilizing oxaliplatin, S-1, and sintilimab. Over a 2-month period of neoadjuvant therapy, the patient's serum α-fetoprotein level significantly decreased from 52,951.56 ng/mL to 241.04 ng/mL. Computed tomography scans revealed substantial tumor regression. Subsequent radical surgical intervention confirmed significant tumor shrinkage, with no evidence of lymph node metastasis upon pathological examination. This is the first report of chemotherapy combined with sintilimab in the treatment of gastric hepatoid adenocarcinoma, which may provide novel insights into the therapeutic strategy for HAS.
2024-10-10 | Surgically treated brain metastases of gastric origin: a case series and systematic review.
The incidence of brain metastases from gastric origin is less than 1% in those with primary gastric cancer. Given this exceedingly rare presentation, there is limited literature describing the outcomes of their neurosurgical treatment. We wish to identify the role of surgical intervention for brain lesions in metastatic gastric cancer via institutional case series and systematic review. This study was divided into two sections: (1) a retrospective, single-center patient series assessing outcomes of neurosurgical treatment modalities in patients with malignancy arising from the stomach with brain metastases and (2) a systematic review abiding by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines between the years of 1980 and 2021 assessing outcomes of patients with primary stomach cancer with metastasis to the brain treated with surgery. Four patients with gastric brain metastases were treated at our institution, and 16 patients were identified in literature from a total of 9 studies and case reports. The mean age at the time of stomach cancer diagnosis was 57.3 years, with a mean time to brain metastases of 14.8 months. The primary gastric cancer was most commonly adenocarcinoma (70%). Patients most presented with single lesions (58%) and were treated with multimodal neurosurgical intervention (65%). Mean overall survival following neurosurgery was 12.45 months. Brain metastases from gastric origin are extremely rare. Surgical resection of metastatic brain lesions should be considered as a treatment modality in surgical candidates. Future attention should be given to the effect of adjuvant therapies and surgical techniques on survival and quality of life.
2023-10-20 | MIR17HG: A Cancerogenic Long-Noncoding RNA in Different Cancers.
LncRNA MIR17HG, located at chromosome 13q31, plays an inevitable role in promoting tumor progressions, such as tumorigenesis, proliferation, and metastasis. Besides, lncRNA MIR17HG is rare due to its open reading frame (ORF), which can be translated to produce protein. By systematically retrieval, we summarized that MIR17HG is an emerging lncRNA that exhibits carcinogenically in osteosarcoma (OS), glioma, cervical squamous cell carcinoma (CSCC), colorectal cancer (CRC), gastric cancer (GC), atypical teratoid rhabdoid tumors (ATRT). Furthermore, a high expression level of MIR17HG protein is also linked with meningioma. Additionally, MIR17HG polymorphisms in glioma, CRC, liver cancer (LC), breast cancer (BC), head and neck squamous cell carcinoma (HNSCC), and multiple myeloma (MM) also have a large influence on cancer susceptibility, prognosis, and so on. Collectively, long non-coding RNA MIR17HG's tumor-stimulative role could be a promising therapeutic target. Besides, by investigating patients' MIR17HG single-nucleotide polymorphisms (SNPs), clinicians could also personalize the productive interventions in gene therapy or predict the diagnosis/prognosis precisely.
2022-05-11 | ATM Germline-Mutated Gastroesophageal Junction Adenocarcinomas: Clinical Descriptors, Molecular Characteristics, and Potential Therapeutic Implications.
Gastroesophageal junction (GEJ) adenocarcinoma is a rare cancer associated with poor prognosis. The genetic factors conferring predisposition to GEJ adenocarcinoma have yet to be identified. We analyzed germline testing results from 23 381 cancer patients undergoing tumor-normal sequencing, of which 312 individuals had GEJ adenocarcinoma. Genomic profiles and clinico-pathologic features were analyzed for the GEJ adenocarcinomas. Silencing of ATM and ATR was performed using validated short-interfering RNA species in GEJ, esophageal, and gastric adenocarcinoma cell lines. All statistical tests were 2-sided. Pathogenic or likely pathogenic ATM variants were identified in 18 of 312 patients (5.8%), and bi-allelic inactivation of ATM through loss of heterozygosity of the wild-type allele was detected in all (16 of 16) samples with sufficient tumor content. Germline ATM-mutated GEJ adenocarcinomas largely lacked somatic mutations in TP53, were more likely to harbor MDM2 amplification, and harbored statistically significantly fewer somatic single nucleotide variants (2.0 mutations/Mb vs 7.9 mutations/Mb; P < .001). A statistically significantly higher proportion of germline ATM-mutated than ATM-wild-type GEJ adenocarcinoma patients underwent a curative resection (10 [100%] vs 92 [86.8%], P = .04; Fisher's exact test.), A synthetic lethal interaction between short-interfering RNA silencing of ATM and ATR was observed in the models analyzed. Our results indicate that germline pathogenic variants in ATM drive oncogenesis in GEJ adenocarcinoma and might result in a distinct clinical phenotype. Given the high prevalence of germline ATM-mutated GEJ adenocarcinomas, genetic testing for individuals with GEJ adenocarcinomas may be considered to better inform prognostication, treatment decisions, and future cancer risk.
small molecules
2026-09-25 | Case Report: Conversion therapy with chemotherapy, antiangiogenic therapy, and immunotherapy for locally advanced synchronous gastric hepatoid adenocarcinoma and poorly differentiated adenocarcinoma
Hepatoid adenocarcinoma of the stomach (HAS) is a rare, aggressive gastric carcinoma that is frequently associated with elevated alpha-fetoprotein (AFP). We report a patient with resolved hepatitis B virus infection and two spatially distinct gastric lesions: poorly differentiated adenocarcinoma in the gastric body and HAS in the gastric angularis. The disease was initially considered unresectable. After multidisciplinary evaluation, the patient received oxaliplatin, S-1, sintilimab, and apatinib. Treatment produced radiological regression and AFP normalization, enabling total gastrectomy. Histopathology showed no viable carcinoma in either tumor bed or in 20 regional lymph nodes, confirming a pathological complete response. This case illustrates the potential role of individualized conversion therapy in selected patients with alpha-fetoprotein-producing gastric cancer. It does not establish the four-agent regimen as standard care. Interpretation is limited by the single-patient design, short follow-up, absence of lesion-specific sequencing and serial hepatitis B virus DNA data, and a nonstandardized maintenance strategy.
2026-09-18 | Rapidly Progressive Gastric Poorly Differentiated Neuroendocrine Carcinoma Mimicking Gastrointestinal Stromal Tumor: A Case Report.
Poorly differentiated gastric neuroendocrine carcinoma (NEC) represents a rare but highly aggressive malignancy, typically diagnosed at advanced stages, which are associated with poor prognosis. We present a case of a 71-year-old male with a history of distal gastrectomy who developed recurrent gastrointestinal bleeding from a subepithelial gastric mass. The lesion initially measured approximately 2 cm and demonstrated endoscopic and radiological features reminiscent of gastrointestinal stromal tumors (GIST). Repeated endoscopic biopsies indicated weak c-KIT and DOG1 positivity; however, the mass enlarged rapidly to 8 cm within 2 months, accompanied by multiple hepatic metastases. Ultrasound-guided liver biopsy confirmed the diagnosis of poorly differentiated gastric NEC. Cisplatin-based palliative chemotherapy was initiated, but the patient died within 3 weeks due to persistent hemorrhage and rapid clinical decline. Although uncommon, gastric NEC may closely mimic GIST both clinically and pathologically. Accurate differentiation between these entities is essential, given their markedly divergent prognoses and therapeutic approaches.
2026-08-10 | An example of successful combination treatment of a patient with primary multiple synchronous squamous cell carcinoma of the esophagus and squamous cell carcinoma of the stomach
Our work presents an extremely rare case of primary synchronous tumors in the esophagus and stomach with a similar histological type, with a different approach to treatment in a young patient. The high sensitivity of squamous cell carcinoma to drug therapy was vividly reflected in our example and clinically proven in the form of complete tumor resorption in the esophagus. Despite the generally accepted standards of treatment, we were dictated an individual treatment plan, thanks to which we managed to limit ourselves to gastric surgery, thereby avoiding the extended resection stage on the esophagus, thereby maintaining an optimal quality of life.
2026-08-07 | Postoperative Adjuvant Treatment Decision for Early Epstein-Barr Virus-Associated Gastric Cancer.
Epstein-Barr virus-associated gastric cancer (EBVaGC) is a relatively rare clinical subtype. Despite its generally favorable prognosis, preoperative diagnosis remains challenging, and no established consensus exists regarding postoperative adjuvant treatment strategies for early-stage patients with high-risk pathological factors. This study reports a female case of early-stage EBVaGC of the lymphoepithelioma-like carcinoma subtype complicated with perineural invasion (a high-risk factor), and systematically explores the etiology, pathological features, key diagnostic points, individualized adjuvant therapy options, and prognosis of EBVaGC. The aim is to improve clinicians' understanding of this gastric cancer subtype, reduce its misdiagnosis rate, and accelerate the development of standardized diagnostic and treatment pathways. A case of a 60-year-old female patient admitted with "abdominal pain and distension for more than 1 year" was reported, and postoperative pathology confirmed EBVaGC. The clinical manifestations and diagnostic and treatment process were analyzed in combination with a review of relevant literature from recent years. Preoperative gastroscopic biopsy revealed poorly differentiated adenocarcinoma of the gastric mucosa. The patient underwent laparoscopic radical subtotal gastrectomy with lymph node dissection. Postoperative pathology confirmed EBVaGC. After symptomatic treatment, the patient improved and was discharged from the hospital. One month after surgery, no disease progression was observed and the SOX regimen was administered. The patient tolerated the treatment well, and the next cycle of chemotherapy is currently planned. EBVaGC lacks specific clinical manifestations, and laboratory findings may be within normal ranges at the time of onset. Reliance solely on conventional gastroscopy and histopathological biopsy can easily lead to misdiagnosis and inappropriate treatment. Epstein-Barr virus-encoded RNA in situ hybridization is the core diagnostic modality for definitive diagnosis. This subtype generally has a favorable prognosis. However, for patients with high-risk pathological factors such as perineural invasion and tumor invasion into the muscularis propria, standardized postoperative individualized adjuvant therapy should be administered based on tumor stage and molecular profiles.
2026-08-07 | Capmatinib for High-Level MET-Amplified Metastatic Gastric Cancer Identified by Comprehensive Genomic Profiling: A Case Report and Literature Review.
High-level MET gene amplification is a rare but potentially actionable alteration in gastric cancer. Previous phase III trials of MET-targeted therapies enrolled broadly MET-positive populations without prospective selection for high-level MET amplification, and no MET-directed therapy is currently established for this disease. Here, we report a 74-year-old woman with heavily pretreated metastatic gastric adenocarcinoma harboring high-level MET amplification (copy number 21) identified by comprehensive genomic profiling. Following expert panel review, the patient received capmatinib through the BELIEVE trial (NCCH1901; jRCTs031190104) and achieved a confirmed partial response at 8 weeks, with a 43.7% reduction in the sum of target lesion diameters. The response was maintained at 16 weeks; disease progression was observed at 24 weeks, with a progression-free survival of approximately 5.5 months. In the context of a literature review of MET-targeted therapies in gastric cancer, this case supports further investigation of selective MET inhibition in gastric cancer with high-level MET amplification, a rare molecular subset not prospectively enriched in previous clinical trials.
proteins
2025-10-13 | Personalized peptide vaccines induce predicted T cell responses against signet ring cell carcinoma—a case report
T cell-based immunotherapies increasingly include personalized neoantigen vaccines that target tumor-specific mutations. However, despite their promise, current neoantigen vaccines show limited and unpredictable clinical benefit, with T cell responses observed in only a subset of patients. To overcome these limitations, we developed the VERDI (Vaccine Epitopes Ranked by Digital Intelligence) System—a cloud-based computational platform that integrates a patient’s human leukocyte antigen (HLA) class I and II genotype with selected tumor-associated antigens (TAAs), including cancer-testis antigens (CTAs), to identify peptides with high predicted immunogenicity and low risk of immune-related adverse events (irAEs). Using the VERDI System, we designed ten personalized peptide vaccines for a patient with metastatic signet ring cell carcinoma (SRCC), a rare and aggressive gastric cancer with limited treatment options. All ten VERDI vaccines were well tolerated and consistently induced tumor-specific T cell responses following a single administration, without the need for checkpoint inhibitors. The patient survived for 15 months—substantially longer than the reported median survival of 5.6 months in metastatic SRCC—highlighting the potential of this individualized, predictive vaccine platform to improve outcomes in advanced cancer.
2025-06-12 | Last decade of advances in gastric neuroendocrine tumors: Innovations, challenges, and future directions.
Gastric neuroendocrine tumors (G-NETs) are rare tumors originating from enterochromaffin-like cells, with an incidence of 0.4 per 100000 annually. There are three main types: (1) Type I, linked to chronic atrophic gastritis and hypergastrinemia, makes up 75%-80% of G-NETs; (2) Type II, associated with Zollinger-Ellison syndrome (ZES) and multiple endocrine neoplasia, comprises 5%; and (3) Type III, sporadic tumors with a higher metastatic potential, accounting for 15%-25%. Diagnosis involves endoscopy, biopsy, and histological examination. Additional methods include serum gastrin testing, immunohistochemistry, and imaging techniques such as computer tomography or magnetic resonance imaging for detecting metastasis. Type I treatment usually involves endoscopic resection (ER), with surgical resection for recurrence. Somatostatin analogs (SSAs) can reduce tumor size, and the prognosis is generally excellent. Type II treatment centers on surgical removal of the gastrinoma, with ER for smaller lesions and SSAs for symptom management. Type III requires surgical resection (partial or total gastrectomy) with lymph node dissection, and possibly chemotherapy. This type has a worse prognosis due to its aggressive nature. Emerging treatments like Peptide Receptor Radionuclide Therapy are promising for advanced cases, and ongoing research into immunotherapies is expanding future treatment options. Regular endoscopic follow-up is crucial to monitor for recurrence or metastasis across all types. Our literature review explores the current perspectives on G-NETs and highlights the importance of further research to improve diagnostic precision and treatment, particularly for those associated with less favorable cases. To improve diagnostic precision and treatment, particularly for those associated with less favorable cases. A systematic search was conducted in PubMed, Scopus, and Web of Science until September 2024. Two independent reviewers screened titles, abstracts, and full texts for eligibility based on G-NET treatment in adults. Eligible studies included cohort studies, clinical trials, case series, and case reports, while in vitro, pediatric, and non-English studies were excluded. Relevant data were extracted independently, and disagreements were resolved through discussion. Study quality was assessed using appropriate tools. G-NETs are rare, classified into three types: (1) Type I; (2) Type II; and (3) Type III. Type I G-NETs, often associated with chronic atrophic gastritis, are typically slow-growing and low-grade, with favorable outcomes following surgical resection. Type II G-NETs arise in hypergastrinemia conditions like multiple endocrine neoplasia and ZES, showing moderate malignancy risk. Type III G-NETs, the most aggressive and least common, present with distant metastases and poor prognosis. Diagnosis relies on endoscopy, imaging, and biomarkers like chromogranin A. Treatment varies by type, ranging from ER to aggressive surgery and chemotherapy for advanced cases. Regular follow-up is essential to monitor recurrence, particularly for type III G-NETs. G-NETs require tailored diagnosis and treatment based on type and stage. Types I and II generally have better prognosis, while types III and IV are linked to poorer outcomes due to invasion and metastasis. Treatment strategies vary from ER for type I to extensive surgery for type III. Emerging therapies, like somatostatin analogs and peptide-receptor radionuclide therapies, show promise in advanced cases. Further research is essential to improve early diagnosis and treatment, particularly for high-risk lesions.
2023-08-04 | The epigenetic modifier lysine methyltransferase 2C is frequently mutated in gastric remnant carcinoma.
Gastric remnant carcinoma (GRC), which occurs in the stomach after partial gastrectomy, is a rare and aggressive form of gastric adenocarcinoma (GAC). Comprehensive profiling of genomic mutations in GRC could provide the basis for elucidating the origin and characteristics of this cancer. Herein, whole-exome sequencing (WES) was performed on 36 matched tumor-normal samples from patients with GRC and identified recurrent mutations in epigenetic modifiers, notably KMT2C, ARID1A, NSD1, and KMT2D, in 61.11% of cases. Mutational signature analysis revealed a low frequency of microsatellite instability (MSI) in GRC, which was further identified by MSIsensor, MSI-polymerase chain reaction, and immunohistochemistry analysis. Comparative analysis demonstrated that GRC had a distinct mutation spectrum compared to that of GAC in The Cancer Genome Atlas samples, with a significantly higher mutation rate of KMT2C. Targeted deep sequencing (Target-seq) of an additional 25 paired tumor-normal samples verified the high mutation frequency (48%) of KMT2C in GRC. KMT2C mutations correlated with poor overall survival in both WES and Target-seq cohorts and were independent prognosticators in GRC. In addition, KMT2C mutations were positively correlated with favorable outcomes in immune checkpoint inhibitor-treated pan-cancer patients and associated with higher intratumoral CD3+ , CD8+ tumor-infiltrating lymphocyte counts, and PD-L1 expression in GRC samples (p = 0.018, 0.092, 0.047, 0.010, and 0.034, respectively). Our dataset provides a platform for information and knowledge mining of the genomic characteristics of GRC and helps to frame new therapeutic approaches for this disease.
2019-11-19 | KMT2C Mutations in Diffuse-Type Gastric Adenocarcinoma Promote Epithelial-to-Mesenchymal Transition.
Lauren diffuse-type gastric adenocarcinomas (DGAs) are generally genomically stable. We identified lysine (K)-specific methyltransferase 2C (KMT2C) as a frequently mutated gene and examined its role in DGA progression. We performed whole exome sequencing on tumor samples of 27 patients with DGA who underwent gastrectomy. Lysine (K)-specific methyltransferase 2C (KMT2C) was analyzed in DGA cell lines and in patient tumors. KMT2C was the most frequently mutated gene (11 of 27 tumors [41%]). KMT2C expression by immunohistochemistry in tumors from 135 patients with DGA undergoing gastrectomy inversely correlated with more advanced tumor stage (P = 0.023) and worse overall survival (P = 0.017). KMT2C shRNA knockdown in non-transformed HFE-145 gastric epithelial cells promoted epithelial-to-mesenchymal transition (EMT) as demonstrated by increased expression of EMT-related proteins N-cadherin and Slug. Migration and invasion in gastric epithelial cells following KMT2C knockdown increased by 47- to 88-fold. In the DGA cell lines MKN-45 and SNU-668, which have lost KMT2C expression, KMT2C re-expression decreased expression of EMT-related proteins, reduced cell migration by 52% to 60%, and reduced cell invasion by 50% to 74%. Flank xenografts derived from KMT2C-expressing DGA organoids, compared with wild-type organoids, grew more slowly and lost their infiltrative leading edge. EMT can lead to the acquisition of cancer stem cell (CSC) phenotypes. KMT2C re-expression in DGA cell lines reduced spheroid formation by 77% to 78% and reversed CSC resistance to chemotherapy via promotion of DNA damage and apoptosis. KMT2C is frequently mutated in certain populations with DGA. KMT2C loss in DGA promotes EMT and is associated with worse overall survival.
2012-02-13 | Spontaneous complete regression of gastric large-cell neuroendocrine carcinoma: mediated by cytomegalovirus-induced cross-autoimmunity?
Spontaneous regression of malignant tumour is a rare phenomenon. This report describes such an occurrence in a gastric large cell neuroendocrine carcinoma of a 77-year-old man. The patient presented with dyspepsia, and biopsy of the fungating mass in the cardia showed a high grade neuroendocrine carcinoma. The pre-operative biopsy taken after 3 months showed chronic inflammation and cytomegalovirus inclusions, but no tumour. In the gastrectomy specimen, no residual tumour was found. Instead, there were foamy histiocytes, chronic inflammatory cells and fibrovascular tissue splitting apart the muscularis propria. In addition, there was ganglionitis involving the myenteric plexus, even in areas of the stomach away from the inflamed site. Chemotherapy, radiotherapy or alternative medicine (including herbal medicine) had not been given. We postulate that cytomegalovirus infection initiated a cross-autoimmune reaction against neuronal cells, and this reaction "unintentionally" eliminated the carcinoma cells which also expressed neural antigens.
cell therapies
2026-09-06 | Gastric perforation repaired by hepatic round ligament: Case report and literature review.
Gastric perforation is a rare but life-threatening complication of gastric cancer, often presenting with acute peritonitis and requiring emergent surgical repair. The conventional treatment relies on an omental patch (Graham's technique); however, this approach is not always feasible, particularly in patients with advanced disease or omental involvement. We report the case of a 44-year-old male with advanced gastric adenocarcinoma complicated by peritoneal carcinomatosis who presented with acute abdomen following stent insertion. Imaging confirmed gastric perforation and generalized peritonitis. During emergent laparoscopic exploration, the omentum was unsuitable due to carcinomatous infiltration. Instead, the hepatic round ligament was mobilized and used as a patch to seal the perforation, achieving effective closure. The patient initially recovered well postoperatively; however, he later deteriorated due to progression of his underlying malignancy and died on postoperative day 16. This case highlights the hepatic round ligament as a viable alternative to the omentum in repairing gastric perforations, particularly in malignant or hostile abdominal environments. Wider application of this technique warrants further study to establish its safety and long-term outcomes.
2025-09-18 | Clinicopathological Features and Management of Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS).
Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare hereditary gastric cancer syndrome linked to APC promoter IB variants and characterized by gastric polyposis. Its natural history and management are poorly defined. We sought to characterize the clinicopathological features of GAPPS and infer management guidelines. We retrospectively analyzed individuals with GAPPS enrolled in a natural history study from January 2017 to September 2023. Demographics, pathogenic gene variants, endoscopic findings, and histopathology results were studied. Of 21 patients with GAPPS, 11 (52%) were male, and most were non-Hispanic white (71%). Median age at germline genetic testing was 44 years (range 12-75 years), and all individuals had a pathogenic variant in the APC promoter IB. Esophagogastroduodenoscopy (EGD) was performed in almost all patients (91%), with a median age of 37 years (range 12-75 years) at initial EGD. Gastric polyps carpeting the fundus and body with antral sparing were noted in all individuals. Gastric adenocarcinoma (n = 3), high-grade dysplasia (n = 7), low-grade dysplasia (n = 3), and benign fundic gland polyposis (n = 6) were demonstrated on endoscopic biopsies. Then, 43% (9/21) of patients underwent total gastrectomy (TG) at a median age of 44 years (range 15-63 years). Histopathology of final gastrectomy specimens demonstrated more advanced pathology compared with endoscopic biopsies in five of nine patients. Given the challenge of effective endoscopic surveillance owing to extensive polyposis, and the risk of malignant transformation, prophylactic TG should be considered for patients with GAPPS. Longitudinal studies are needed to delineate lifetime cancer risk and clinical management guidelines.
2023-07-31 | CD4-/CD8- double-negative tumor-infiltrating lymphocytes expanded from solid tumor tissue suppress the proliferation of tumor cells in an MHC-independent way.
Tumor-infiltrating lymphocytes (TILs) have shown remarkable clinical responses in some patients with advanced solid tumors. As a rare subset of TILs, CD4-/CD8- double-negative T cells (DNTs) were poorly known. This study aims to investigate the characteristics and function of CD3+CD4-CD8- TILs (double-negative TIL, DN-TILs) derived from solid tumor. DN-TILs were derived and expanded ex vivo from resected gastric carcinoma tissue and phenotyped by flow cytometry. The cytotoxicity of DN-TILs was determined against established tumor cell lines in vitro or through in vivo adoptive transfer into xenograft models. K562 cells were transferred with the HLA gene to verify whether the cytotoxicity of DN-TILs was MHC-independent. Flow cytometric analysis revealed a high-purity population of DN-TILs (> 97%) within CD3+ TILs, which expanded more than 800-folds in 2 weeks, consisting of a mixture of alpha-beta (αβ) and gamma-delta (γδ) T-cell receptor (TCR)-expressing cells (with the majority being αβ-TCR, > 95%). Using single-cell RNA sequencing, the expanded DN-TILs were categorized into four main subsets, Natural Killer T cells (approximately 80%, 5563 in 7028), Progenitor cells, Germ cells and T helper2 cells. DN-TILs exhibited a broad anticancer cytotoxicity in a donor-unrestricted manner against various cancer cell lines derived from pancreatic cancer (Panc-1), gastric cancer (HGC-27), ovarian cancer (SKOV-3), malignant melanoma (A375). The cytotoxicity was MHC-independent, which was not altered in K562 transferring with HLA gene or not. DN-TILs significantly reduced tumor volume in xenograft models with superior tumor-homing ability and low off-target toxicity. Gastric carcinoma derived DN-TIL can target tumor cells in vitro and in vivo. DN-TILs have the potential to be used as a adoptive cell therapy for solid cancers with both the advantages of DNT and TIL.
2022-12-02 | Therapeutic plasma exchange in gastric signet ring cell carcinoma presenting as microangiopathic hemolytic anemia: A rare case report.
Microangiopathic hemolytic anemia (MAHA) defines a group of disorders characterized by the formation of microthrombi in capillaries and arterioles and the fragmentation of erythrocytes that pass through. Cancer-related MAHA is a rare but serious condition that is encountered in patients diagnosed with a malignancy. This clinical picture is thought to be linked to certain tumor characteristics; particularly, adenocarcinoma histology, vascular invasion, and bone marrow infiltration. MAHA is most commonly associated with tumors of gastric, prostate, and breast origin. The optimal treatment is not clear; however, there is evidence for the importance of promptly starting an effective antineoplastic regimen and it was also reported that administering therapeutic plasma exchange (TPE) therapy for immunocomplex removal could be beneficial for patients with symptoms of bleeding and thrombosis. Here, we present a case that presented a picture of MAHA secondary to gastric signet-ring cell adenocarcinoma (SRCC). The clinical picture was initially evaluated as thrombotic thrombocytopenic purpura and the patient benefited significantly from the TPE treatment administered before the adenocarcinoma diagnosis was confirmed. In this period, epistaxis stopped, platelet count increased from 25 × 109 /L to 162 × 109 /L, fragmented erythrocyte rate in the peripheral smear decreased by more than 75% and other laboratory findings of hemolysis (LDH, bilirubin, etc.) significantly improved.
2022-03-08 | Filling in the "GAPPS": an unusual presentation of a child with gastric adenocarcinoma and proximal polyposis of the stomach.
Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a very rare gastric polyposis syndrome characterized by numerous polyps of the gastric fundus and body. We present the unusual case of a 10-year-old Polish-American male with history of eosinophilic esophagitis, who was found to have multiple fundic gland polyps (FGP) with low grade dysplasia on esophagogastroduodenoscopy. Subsequent evaluation including genetic testing confirmed the diagnosis of GAPPS, and after exhaustive multidisciplinary consultation the decision was made to proceed with prophylactic total gastrectomy given the markedly increased risk of gastric adenocarcinoma in GAPPS patients. To our knowledge, this represents the youngest patient diagnosed with GAPPS and the youngest patient who has undergone prophylactic gastrectomy for this disease at age 8 and 10 years, respectively. The pathophysiology, presentation, and treatment of GAPPS in a pediatric patient are discussed.
antibodies
2026-09-23 | Successful non-surgical management of locally advanced gastric adenocarcinoma with squamous differentiation and programmed death-ligand 1 combined positive score 75: a case report.
Poorly differentiated gastric adenocarcinoma with squamous differentiation is a rare and aggressive malignancy, with limited representation in the literature. Its biological behaviour remains poorly characterized, and prognosis is generally poor. Here, we present a case that highlights the role of biomarker-driven, non-surgical management in advanced gastric malignancy, particularly in the context of high PD-L1 expression in an elderly patient. A 75-year-old Syrian Arab male presented with anaemia, weight loss and anorexia. Imaging revealed a large ulcerated gastric mass measuring 9 × 11 cm with perigastric lymphadenopathy and local invasion, but no evidence of distant metastasis. Histopathological examination confirmed poorly differentiated adenocarcinoma with squamous differentiation. Immunohistochemistry demonstrated diffuse p40 positivity and focal cytokeratin 7 (CK7) positivity. Notably, programmed death-ligand 1 (PD-L1) expression was strongly positive, with a combined positive score (CPS) of 75. The patient was started on combined chemotherapy (oxaliplatin and 5-fluorouracil) and immunotherapy (nivolumab). Remarkably, follow-up positron emission tomography-computed tomography (PET-CT) at 3 months showed a reduction in tumour size and metabolic activity, with near complete radiological remission by 6 months. At 1-year follow-up, the patient remains clinically well and disease-free without surgical intervention. This case illustrates how high PD-L1 expression may substantially alter the expected clinical course of gastric cancer, even in rare and poorly differentiated subtypes typically associated with poor outcomes. The observed durable clinical complete response underscores the potential of biomarker-guided chemo-immunotherapy and supports consideration of non-surgical approaches in selected patients.
2026-08-13 | Case Report: Synchronous Esophageal Squamous Cell Carcinoma and Gastric Cardia Adenocarcinoma with Hepatoid Differentiation After Neoadjuvant Chemoimmunotherapy.
Background/Objectives: Hepatoid adenocarcinoma is a rare adenocarcinoma subtype. Synchronous esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma with hepatoid differentiation is exceptionally uncommon. This report describes lesion-specific staging, pathological response assessment, and individualized management after neoadjuvant chemoimmunotherapy. Methods: De-identified clinical, imaging, laboratory, operative, and pathological data were retrospectively reviewed. Both lesions were staged according to the AJCC 8th edition and reassessed using the CAP modified Ryan four-tier tumor regression grading system. Results: A 61-year-old man presenting with dysphagia had separate ESCC and gastric cardia adenocarcinoma, both staged cT2N0M0. One cycle of pembrolizumab 200 mg, nab-paclitaxel 300 mg, and cisplatin 100 mg was administered. Agranulocytosis precluded further neoadjuvant therapy; after neutrophil recovery, R0 resection was performed. Pathological review showed ESCC ypT1aN0M0, score 1, and cardia adenocarcinoma ypT1aN0M0, score 3, with approximately 30% regional hepatoid differentiation. All 10 examined lymph nodes were negative. AFP was not measured before treatment; post-treatment/preoperative values were 14.45 and 14.68 ng/mL, and the postoperative value was 6.08 ng/mL. Postoperative tislelizumab monotherapy was selected as an individualized, non-standard strategy, mainly because of affordability. At approximately 6 months after surgery, no recurrence, metastasis, or maintenance-related adverse event was identified. Conclusions: This case emphasizes biopsy under-sampling and lesion-specific staging and pathological assessment. The regression-score difference is descriptive and confounded by baseline burden, histology, and one-cycle exposure; the AFP findings do not validate a surveillance biomarker.
2026-07-03 | MET Expression in Upper Gastrointestinal Adenocarcinoma: Prevalence, Prognostic Impact, and Implications for Anti-MET Antibody-Drug Conjugate Therapy.
MET is an actionable receptor tyrosine kinase, and MET-directed antibody-drug conjugates (ADCs) have recently entered clinical practice with FDA approval in non-small cell lung cancer and are now being evaluated across gastrointestinal malignancies, with patient selection based on MET immunohistochemistry (IHC) 3+ membranous staining at varying percentage thresholds. However, robust real-world data on MET protein expression and clinically relevant ADC-aligned thresholds in upper GI adenocarcinomas remain limited. We profiled 1532 upper GI adenocarcinomas using the clinically validated VENTANA MET (SP44) IHC assay. MET was stratified by (i) 3+ membranous staining fractions (any, ≥ 10%, ≥ 50%) reflecting contemporary ADC eligibility concepts and (ii) H-score (0-300; high ≥ 150). Overall survival analyses and multivariable Cox regression analyses were performed. High MET expression was uncommon (H-score ≥ 150: 2.3%; any 3+: 1.6%; ≥ 10% 3+: 1.3%; ≥ 50% 3+: 1.0%) and enriched in advanced T stage. MET IHC strongly predicted MET amplification (H-score ≥ 150: 63.6% amplified vs. 2.4% in negatives; any 3+: 75.0% vs. 2.6%; all p < 0.001). Any MET 3+ staining was independently associated with inferior overall survival (adjusted HR 2.22, 95% CI 1.29-3.83). Most MET 3+ tumors lacked concurrent HER2 positivity, Claudin-18.2 expression, or dMMR/MSI. In the largest real-world cohort to date, MET overexpression identifies a rare, biologically aggressive subset with poor outcomes. By applying the latest MET-ADC-relevant IHC criteria (including the ≥ 10% 3+ threshold), this study provides clinically translatable prevalence estimates and supports standardized MET testing to inform prospective MET-directed ADC trials in upper GI adenocarcinoma.
2026-05-28 | Multi-omics approaches to unveil the mixed molecular characteristics of hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation.
e16109 Background: Hepatoid adenocarcinoma of stomach with neuroendocrine differentiation (HAS-NEC) is an extremely rare subtype of gastric cancer, and there is currently no systematic research focused on this uncommon subtype. This study aims to investigate the clinicopathological and molecular characteristics of this rare subtype, thereby providing a reference for precision therapy for such patients. Methods: We retrospectively collected tumor tissue and adjacent carcinoma tissue samples from 84 patients, along with corresponding clinicopathological information, for whole exome sequencing and transcriptome sequencing. Spearman correlation analysis and unsupervised clustering analysis were employed to explore the molecular characteristics of HAS-NEC and to assess the similarities and differences among the various sample groups. Results: From the perspective of clinical pathological features, HAS-NEC exhibited greater similarity to HAS patients, with no significant differences in all clinicopathological characteristics. HAS-NEC patients possessed distinct genomic features compared to both HAS and NEC patients, with TTN being the most frequently mutated gene, occurring in 90% of cases. Mutations in TET1 were exclusive to HAS-NEC patients and were not detected in the other two groups. At the transcriptional level, HAS-NEC patients showed greater similarity to HAS patients, demonstrating more comparable transcriptional expression patterns. Lastly, we identified a potential therapeutic target, ZFHX4, whose mutations influence the transcriptional expression and prognosis of gastric cancer patients, further impacting immune infiltration and response to immunotherapy. Conclusions: Patients with HAS-NEC exhibited unique molecular biological characteristics that could not be simply viewed as a combination of HAS and NEC.
2026-02-23 | Long-term durable response to Sintilimab therapy in synchronous lung squamous cell carcinoma and gastric adenocarcinoma: a rare case report.
Gastric cancer (GC) and lung squamous cell carcinoma (SCC) are major global causes of cancer-related morbidity and mortality, but their synchronous occurrence is exceedingly rare and poses substantial diagnostic and therapeutic challenges. This report describes a 64-year-old male with synchronous lung SCC and gastric adenocarcinoma who achieved long-term disease control with Sintilimab monotherapy. Initial imaging and biopsy confirmed poorly differentiated lung SCC (PD-L1 CPS: 2), while PET-CT and endoscopy identified a gastric lesion later confirmed as adenocarcinoma (PD-L1 CPS: 5). Despite indications for chemotherapy, the patient declined cytotoxic therapy and initially refused surgery. He was treated with Sintilimab plus Anlotinib, resulting in lung lesion regression. Progression of gastric obstruction led to gastrectomy two years later; subsequent lung recurrence was managed surgically. Both tumors showed high proliferative indices (Ki-67 ~80-90%) and PD-L1 expression, supporting responsiveness to immune checkpoint blockade. This case highlights the feasibility of immune monotherapy in managing complex synchronous malignancies, especially when standard treatments are declined.
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2025-09-09 | Pediatric Alpha-Fetoprotein-Producing Gastric Cancer Presenting With Dysphagia and Multiple Liver Tumors.
Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) is resistant to chemotherapy and is associated with poor prognosis. Pediatric gastric cancer has an incidence of 0.02% among gastric cancer patients, with a median survival of 5 months. A 13-year-old boy presented with progressive dysphagia for 2 months, accompanied by loss of appetite and significant weight loss. Liver dysfunction and multiple lesions were observed. Laboratory investigations revealed elevated liver enzymes and tumor markers, including AFP, at 24 502 ng/mL. Computed tomography (CT) showed thickening of the gastric cardia and multiple liver lesions. Upper gastrointestinal endoscopy revealed a type 2 tumor in the cardia. Histopathology confirmed adenocarcinoma, and immunohistochemical staining was positive for AFP, establishing a diagnosis of AFPGC with liver metastases (Stage IV). Given the unresectable and HER2-negative nature of the cancer, chemotherapy with TS-1 and cisplatin was initiated, resulting in a temporary reduction in AFP levels and tumor size. However, disease progression was noted after 3 months, requiring a switch in treatment to ramucirumab, paclitaxel, bleomycin, etoposide, cisplatin, or a study drug. Despite these efforts, the patient succumbed to the disease 16 months after initial treatment. AFPGC in children is extremely rare, with few reported cases. The 16-month survival observed in this case exceeds previously reported durations (8 and 4 months). Systematic evaluation of persistent gastrointestinal symptoms enabled earlier diagnosis. Standard adult gastric cancer treatment protocols appeared more effective than AFP-tumor-specific regimens, suggesting they may be optimal for pediatric AFPGC as well. Early diagnosis through detailed history-taking and prompt endoscopic examinations in children with gastrointestinal symptoms may lead to significantly prolonged survival and improved management in this rare malignancy.
2025-01-23 | Hepatoid adenocarcinoma of the stomach with ideal response to neoadjuvant chemo-immunotherapy: a case report.
Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer characterized by histological features resembling hepatocellular carcinoma. Surgical intervention remains the preferred treatment modality for eligible patients. However, the efficacy of neoadjuvant therapy and alternative treatment regimens has been found to be suboptimal. Consequently, due to the high metastatic potential and unfavorable biological behavior of HAS, the prognosis for affected patients is exceedingly poor. We present a case involving a 64-year-old male diagnosed with advanced HAS, who demonstrated significant antitumor responses following a preoperative regimen of chemotherapy combined with immunotherapy, specifically utilizing oxaliplatin, S-1, and sintilimab. Over a 2-month period of neoadjuvant therapy, the patient's serum α-fetoprotein level significantly decreased from 52,951.56 ng/mL to 241.04 ng/mL. Computed tomography scans revealed substantial tumor regression. Subsequent radical surgical intervention confirmed significant tumor shrinkage, with no evidence of lymph node metastasis upon pathological examination. This is the first report of chemotherapy combined with sintilimab in the treatment of gastric hepatoid adenocarcinoma, which may provide novel insights into the therapeutic strategy for HAS.
2024-10-10 | Surgically treated brain metastases of gastric origin: a case series and systematic review.
The incidence of brain metastases from gastric origin is less than 1% in those with primary gastric cancer. Given this exceedingly rare presentation, there is limited literature describing the outcomes of their neurosurgical treatment. We wish to identify the role of surgical intervention for brain lesions in metastatic gastric cancer via institutional case series and systematic review. This study was divided into two sections: (1) a retrospective, single-center patient series assessing outcomes of neurosurgical treatment modalities in patients with malignancy arising from the stomach with brain metastases and (2) a systematic review abiding by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines between the years of 1980 and 2021 assessing outcomes of patients with primary stomach cancer with metastasis to the brain treated with surgery. Four patients with gastric brain metastases were treated at our institution, and 16 patients were identified in literature from a total of 9 studies and case reports. The mean age at the time of stomach cancer diagnosis was 57.3 years, with a mean time to brain metastases of 14.8 months. The primary gastric cancer was most commonly adenocarcinoma (70%). Patients most presented with single lesions (58%) and were treated with multimodal neurosurgical intervention (65%). Mean overall survival following neurosurgery was 12.45 months. Brain metastases from gastric origin are extremely rare. Surgical resection of metastatic brain lesions should be considered as a treatment modality in surgical candidates. Future attention should be given to the effect of adjuvant therapies and surgical techniques on survival and quality of life.
2023-10-20 | MIR17HG: A Cancerogenic Long-Noncoding RNA in Different Cancers.
LncRNA MIR17HG, located at chromosome 13q31, plays an inevitable role in promoting tumor progressions, such as tumorigenesis, proliferation, and metastasis. Besides, lncRNA MIR17HG is rare due to its open reading frame (ORF), which can be translated to produce protein. By systematically retrieval, we summarized that MIR17HG is an emerging lncRNA that exhibits carcinogenically in osteosarcoma (OS), glioma, cervical squamous cell carcinoma (CSCC), colorectal cancer (CRC), gastric cancer (GC), atypical teratoid rhabdoid tumors (ATRT). Furthermore, a high expression level of MIR17HG protein is also linked with meningioma. Additionally, MIR17HG polymorphisms in glioma, CRC, liver cancer (LC), breast cancer (BC), head and neck squamous cell carcinoma (HNSCC), and multiple myeloma (MM) also have a large influence on cancer susceptibility, prognosis, and so on. Collectively, long non-coding RNA MIR17HG's tumor-stimulative role could be a promising therapeutic target. Besides, by investigating patients' MIR17HG single-nucleotide polymorphisms (SNPs), clinicians could also personalize the productive interventions in gene therapy or predict the diagnosis/prognosis precisely.
2022-05-11 | ATM Germline-Mutated Gastroesophageal Junction Adenocarcinomas: Clinical Descriptors, Molecular Characteristics, and Potential Therapeutic Implications.
Gastroesophageal junction (GEJ) adenocarcinoma is a rare cancer associated with poor prognosis. The genetic factors conferring predisposition to GEJ adenocarcinoma have yet to be identified. We analyzed germline testing results from 23 381 cancer patients undergoing tumor-normal sequencing, of which 312 individuals had GEJ adenocarcinoma. Genomic profiles and clinico-pathologic features were analyzed for the GEJ adenocarcinomas. Silencing of ATM and ATR was performed using validated short-interfering RNA species in GEJ, esophageal, and gastric adenocarcinoma cell lines. All statistical tests were 2-sided. Pathogenic or likely pathogenic ATM variants were identified in 18 of 312 patients (5.8%), and bi-allelic inactivation of ATM through loss of heterozygosity of the wild-type allele was detected in all (16 of 16) samples with sufficient tumor content. Germline ATM-mutated GEJ adenocarcinomas largely lacked somatic mutations in TP53, were more likely to harbor MDM2 amplification, and harbored statistically significantly fewer somatic single nucleotide variants (2.0 mutations/Mb vs 7.9 mutations/Mb; P < .001). A statistically significantly higher proportion of germline ATM-mutated than ATM-wild-type GEJ adenocarcinoma patients underwent a curative resection (10 [100%] vs 92 [86.8%], P = .04; Fisher's exact test.), A synthetic lethal interaction between short-interfering RNA silencing of ATM and ATR was observed in the models analyzed. Our results indicate that germline pathogenic variants in ATM drive oncogenesis in GEJ adenocarcinoma and might result in a distinct clinical phenotype. Given the high prevalence of germline ATM-mutated GEJ adenocarcinomas, genetic testing for individuals with GEJ adenocarcinomas may be considered to better inform prognostication, treatment decisions, and future cancer risk.
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Drug Discovery Landscape
16 orphan drug designations for Rare carcinoma of stomach, including 1 approved therapy.
16 orphan drug designations for Rare carcinoma of stomach, including 1 approved therapy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Sonesitatug vedotin | antibodies | EMA | AstraZeneca AB | |
bispecific antibody-drug conjugate produced by conjugating an asymmetric bispecific antibody against human EGFR and TROP2 to a DNA topoisomerase I inhibitor payload | antibodies | FDA | — | Xadcera Biopharmaceutical (Suzhou) Co., Ltd. |
an engineered immunoglobulin variable (IgV) domain of human SIRPalpha fused to human IgG4 Fc protein | proteins | FDA | — | FBD Biologics Limited |
Domvanalimab | antibodies | EMA | Gilead Sciences Ireland Unlimited Company | |
Zimberelimab | antibodies | EMA | Gilead Sciences Ireland Unlimited Company | |
a bispecific antibody composed of a Light Chain and a Heavy Chain pair targeting HER2, and a Light Chain and a Heavy Chain pair targeting CD47 | antibodies | FDA | D3 Bio (Wuxi) Co., Ltd. | |
Bispecific antibody against CLDN18.2 and T cell receptor complex CD3 | antibodies | FDA | Astellas Pharma Global Development, Inc. | |
an anti-Claudin 18.2 monoclonal antibody conjugated with MMAE payload | antibodies | FDA | AstraZeneca | |
FC-fusion bispecific antibody targeting extracellular domains II and IV of HER 2 and FC-fusion bispecific IgG1 antibody inhibiting PD-L1 and CTLA-4 | antibodies | FDA | Jiangsu Alphamab Biopharmaceuticals Co., Ltd. | |
avelumab | antibodies | FDA | EMD Serono Research & Development Institute, Inc. | |
trifluridine/tipiracil [LONSURF] | small molecules | FDA | Approved | Taiho Oncology, Inc. |
masitinib mesylate | small molecules | FDA | AB Science | |
Ipatasertib | small molecules | FDA | Genentech, Inc. | |
trastuzumab emtansine | antibodies | FDA | Genethech, Inc. | |
lapatinib | small molecules | FDA | Novartis Pharmaceuticals Corp. | |
Floxuridine, FUDR | small molecules | FDA | Franco Muggia, M.D. |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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