RARE DISEASE
Giant cell tumor of bone
Giant cell tumor of bone
Giant cell tumor of bone
Synonyms: GCT of bone, Osteoclastoma
Synonyms: GCT of bone, Osteoclastoma
Synonyms: GCT of bone, Osteoclastoma
Drug discovery
1
drug
With orphan designation
Overview
Giant cell tumor of bone (GCTB) is a benign but locally aggressive neoplasm composed of mononuclear stromal cells and osteoclast-like giant cells. Typically arising in the epiphysis of long bones (e.g., distal femur, proximal tibia), it primarily affects skeletally mature individuals aged 20–40 years. While GCTB rarely metastasizes (1–3% to lungs), it causes significant bone destruction and has recurrence rates of 15–50% after treatment. Diagnosis relies on imaging (lytic lesions with "soap bubble" appearance) and histopathology [1][4][6][9].
Burden
Local destruction causes pathological fractures (10–30%) and joint dysfunction [4][6][12]
Recurrence: 25–50% after curettage; 5–15% after wide resection [3][9][16]
Economic/QoL impact: Multiple surgeries common (median 2 procedures); 10-year survival drops to 70% with malignant transformation [8][9][13]
Therapies
Surgical: Curettage with adjuvants (phenol, bone cement) ± preoperative denosumab (RANKL inhibitor) to reduce tumor size [3][8][10]. Wide resection reserved for complex cases (pelvis/spine) or recurrence [8][12]
Medical: Denosumab (FDA-approved) for unresectable/metastatic disease, though associated with rebound recurrence post-treatment [3][13][19]
Adjuncts: Embolization for sacral tumors; radiotherapy limited due to malignant transformation risk [5][8][12]
Categories: rare bone diseases, rare neoplastic diseases
Research Papers
1,872 drug discovery papers about Giant cell tumor of bone, with 3 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,872 drug discovery papers about Giant cell tumor of bone, with 3 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
cell therapies
2026-08-07 | Intralesional resection and autologous fibular graft reconstruction for a giant cell tumor of the fourth metacarpal with a secondary aneurysmal bone cyst: a case report
Introduction and importance: Giant cell tumor (GCT) of bone rarely involves the metacarpal bones. Secondary aneurysmal bone cyst (ABC) changes arising in association with GCT create distinct diagnostic and therapeutic challenges in this uncommon skeletal location. Case presentation: A 21-year-old right-hand-dominant female presented with progressive right fourth metacarpal pain and swelling following minor trauma. Radiographs and magnetic resonance imaging (MRI) demonstrated an expansile osteolytic lesion with cortical thinning and internal fluid–fluid levels suggesting GCT with secondary ABC changes. Preoperative chest radiography showed no evidence of pulmonary metastasis. Intralesional resection was performed while preserving the metacarpal head articular surface. Biological reconstruction was achieved using a non-vascularized autologous fibular graft stabilized with Kirschner wires. Histopathological examination confirmed GCT associated with secondary ABC changes and excluded telangiectatic osteosarcoma. At the 6-month follow-up, the patient demonstrated satisfactory graft incorporation, excellent hand function, and no evidence of local recurrence or pulmonary metastasis. Clinical discussion: Hand GCTs exhibit more aggressive behavior and higher recurrence rates than those in conventional skeletal locations. Differentiating secondary ABC from primary ABC and from telangiectatic osteosarcoma is essential, as treatment strategies and oncological implications differ significantly. Conclusion: Intralesional resection followed by biological reconstruction using a non-vascularized autologous fibular graft preserves hand function while achieving satisfactory early local disease control in selected patients.
2026-07-10 | Short-term Functional Outcomes of Shoulder Girdle Limb Salvage in Primary Bone Tumors: A 2-year Follow-up Study.
The shoulder girdle, encompassing the proximal humerus, scapula, lateral third of the clavicle, and surrounding soft tissues, is the third most frequent site for bone tumors. The proximal humerus is the most commonly affected area, followed by the scapula and clavicle. Managing malignant or aggressive benign bone tumors in this region is particularly challenging due to the proximity to vital neurovascular structures and the need to maintain both stability and dexterity in the shoulder. While traditional treatment often involved extensive resections, contemporary limb salvage techniques focus on preserving function while ensuring effective tumor control. This prospective study included 18 patients who underwent various limb salvage procedures at the Department of Orthopaedics, Vydehi Institute of Medical Sciences and Research Centre in Bengaluru between 2012 and 2019, with a minimum follow-up of 2 years. Diagnosis and staging were performed using imaging modalities and core needle biopsies, with musculoskeletal tumors staged according to the Enneking System. Functional outcomes were assessed using the Musculoskeletal Tumor Society Rating Scale (MSTS). Surgical techniques varied and included endoprosthetic reconstruction, arthrodesis with fibular grafting and plating, and plate fixation with primary shortening. Among the 18 patients, the majority (61%) had giant cell tumors, followed by aneurysmal bone cysts (17%), chondrosarcoma (11%), and osteosarcoma (11%). Functional outcomes, as measured by the MSTS, showed a 75% satisfactory rate. The study population was composed of 55.56% males and 44.44% females. Key parameters evaluated included pain, functional activity, hand positioning, dexterity, lifting ability, and emotional acceptance. Limb salvage surgery for primary bone tumors of the shoulder girdle offers favorable functional outcomes and represents a viable alternative to amputation. Modern reconstruction techniques, such as endoprosthetic reconstruction and fibular grafting with plating, achieve satisfactory results in both function and appearance. The MSTS scoring system is an effective tool for assessing postoperative functional status, and there is a growing preference for less aggressive surgical techniques that preserve limb function while ensuring tumor control.
2026-06-17 | Optimal management of giant cell tumor in the tibial plateau: A case report on curettage and cement reinforcement.
Giant cell tumor of bone (GCTB) is a benign yet locally aggressive neoplasm that commonly arises in the epiphyseal metaphyseal region of long bones, particularly around the knee, where management is challenged by the need to achieve complete tumor excision while preserving joint function in young, active individuals. We describe a 26-year-old female who presented with acute left knee pain and mechanical locking after squatting during exercise. Imaging demonstrated a well-defined 1.7 × 1.7 × 1.7 cm eccentric lesion in the posterior medial tibial plateau with minimal cortical breakthrough and surrounding marrow edema, and CT guided biopsy confirmed the diagnosis of GCTB. She underwent surgery through a posterior Löbbenhofer approach, including meticulous curettage, high speed burring, and phenol application. To shield the articular cartilage from the thermal effects of PMMA cement and avoid long term subchondral stiffness, a protective layer of autologous morselized bone graft was interposed between the cement and the joint surface. Recovery was uneventful, and this single-stage technique provided definitive management with no need for further surgery, ensuring structural support while minimizing recurrence risk. This case highlights the value of combining extended curettage with a graft cement interface to optimize joint preservation in periarticular GCTB and underscores the need for future studies evaluating long term radiological and functional outcomes of such hybrid reconstructions.
2026-06-11 | A Rare Case of Giant Cell Tumor of the First Metatarsal: En Bloc Resection and Fibular Autograft Reconstruction.
Giant cell tumors (GCTs) of bone are benign but locally aggressive neoplasms that predominantly involve the epiphyseal regions of long bones, with the first metatarsal being an exceptionally rare site of involvement. This case report describes the clinical presentation, diagnostic evaluation, surgical management, and functional outcomes of a rare GCT involving the first metatarsal bone. A 54-year-old female presented with a 5-month history of progressive pain and swelling of the right foot localized over the first metatarsal region. Clinical examination revealed a firm, tender, bony expansion measuring approximately 3 × 5 × 3 cm. Radiological investigations, including plain radiography, multiplanar MRI and CT imaging confirmed an osteolytic, expansile lesion suggestive of GCT. En bloc resection of the tumor-bearing segment was performed with reconstruction using non-vascularized fibular autograft fixation with K-wires. Histopathological examination confirmed the diagnosis of GCT of bone. The patient achieved complete surgical resection with excellent functional recovery at 12-month follow-up. The fibular autograft demonstrated satisfactory integration without evidence of recurrence or significant complications. Functional outcome scores improved significantly, and the patient resumed normal weight-bearing activities. Although rare, GCT of the first metatarsal should be considered in the differential diagnosis of expansile osteolytic lesions in the foot. En bloc resection with non-vascularized fibular autograft reconstruction provides oncologically sound treatment with acceptable functional outcomes and minimal recurrence rates. This case underscores the importance of multimodal imaging, histopathological confirmation, and meticulous surgical planning in managing this challenging presentation.
2026-06-11 | Giant Cell Tumor of the Metacarpal Treated with Non-Vascularized Bone Graft: A Case Report.
Giant cell tumor (GCT) of bone is a benign but locally aggressive neoplasm, most commonly affecting the epiphyseal region of long bones. Involvement of the hand bones is rare and is known to exhibit more aggressive behavior with higher recurrence rates compared to conventional sites. Optimal reconstruction following tumor excision in the hand remains challenging, as, along with the reconstruction of the bone defect, the function of the hand should also be addressed. A 19-year-old right-hand-dominant female presented with a progressively enlarging, painful swelling over the dorsum of the right hand. Radiological evaluation revealed an expansile, lytic lesion involving the ring finger metacarpal with cortical breach. Magnetic resonance imaging showed an aggressive lesion with soft-tissue involvement. Histopathological examination confirmed the diagnosis of GCT of bone. The patient underwent wide excision of the tumor followed by reconstruction using a non-vascularized autologous cortical bone graft from the ulna. GCT of the metacarpal is rare and requires aggressive surgical management due to its high recurrence potential. Non-vascularized ulnar bone graft provides a reliable, simple, and effective reconstructive option following tumor excision.
small molecules
2026-07-10 | A Rare Case of Giant Cell tumor of Bone in Distal Tibia.
Giant cell tumors of bone commonly seen in the distal femur, proximal tibia and distal radius and are seen in the age group of 20-40 years with female preponderance. Being close to the joint, the management is formidable, and there are no clinical, radiological or histological parameters to predict chances of recurrence or metastasis. Here, we present a rare case of giant cell tumor of the distal tibia treated successfully with no recurrence at the end of 4 years. A 33-year-old female presented with complaints of pain, swelling and decreased range of motion (ROM) at the left ankle joint for 6 weeks. On examination, we observed swelling and tenderness on left ankle joint with decreased ROM. X-rays and computed tomography revealed a well-defined expansile osteolytic lesion in the distal epiphysio-metaphyseal region of the left tibia without breach in the tibial cortex or ankle joint. Surgery by extensive curettage, adjuvants, cementation and prophylactic fixation was performed. Oral alendronate was started and continued for 24 months after surgery. The patient at 4-year follow-up is doing well, walking without pain, able to squat, having full ROM of the ankle joint with no signs of recurrence.
2026-07-01 | ICG-based NIR fluorescence imaging can help to detect residual giant cell tumor of bone after intralesional curettage: Results of two-year follow-up.
Identification of clinical occult tumor residuals is crucial during giant cell tumor (GCT) intralesional curettage. This study investigated the capacity of indocyanine green (ICG) fluorescence imaging to detect tumor residual during intralesional curettage of GCT. Clinical data of 20 patients with GCT who received ICG near-infrared (NIR) fluorescence-assisted intralesional curettage with a minimal two-year follow-up in our institute were reviewed. Tumors were initially curetted under white light with naked eyes. Then, wounds were scanned to detect fluorescence residuals. Biopsies were conducted on the sites with fluorescence positivity or negativity. The fluorescence intensity (FI) of biopsied samples were determined using standardized process, and samples were sent for pathological examination. All the tumors were successfully stained (100%). One patient (5%) experienced a local recurrence. The overall accuracy of ICG fluorescence in detecting tumor residuals (true positivity and true negativity) was 68%. The false positive rate and false negative rate were 38% and 21%, respectively. Fluorescence-positive samples showed a significantly higher rate of pathological positivity than negative samples (P = 0.001). The meanFI and maxFI of samples with pathological positivity were significantly higher than those with pathological negativity (P value was 0.001 and 0.002, respectively). The AUCROC values for meanFI and maxFI predicting pathological results were 0.713 and 0.719, respectively. ICG-based NIR fluorescence imaging can detect residual GCT after intralesional curettage, and can be used as a supplement to extended curettage to reduce recurrence. The FI is positively related to pathological results. However, false signals may occur. Efforts to increase accuracy and confirm its clinical benefits in preventing recurrence are still needed.
2026-06-08 | A Review of Endovascular Techniques as Therapy for Inoperable Giant Cell Bone Tumors of the Sacrum, Pelvis, and Spine
Abstract Giant cell tumor (GCT) of bone is a benign but locally aggressive neoplasm. Lesions in the sacrum, pelvis, and spine present surgical challenges due to complex anatomy. Selective arterial embolization (SAE) is a minimally invasive treatment option for inoperable GCTs. A narrative review of PubMed and Embase (1976–2024) identified studies that included patients with biopsy-proven GCTs of the sacrum, pelvis, or spine treated with SAE. Inclusion required non-surgical candidacy, treatment with SAE alone, or SAE with denosumab and/or radiotherapy. Studies involving GCTs of the extremities, surgical resection, or preoperative embolization were excluded. Outcomes that were assessed included clinical and radiographic response, recurrence, and complications. Among 70 patients, SAE alone showed 86% (25/29) clinical and 79% (23/29) radiographic response rates. SAE with radiotherapy showed a higher clinical and radiographic response than SAE with denosumab (83% clinical and 65% radiographic versus 39% clinical and 50% radiographic). Recurrence and metastasis varied across groups. SAE is an effective therapy for inoperable GCTs of the axial skeleton. Further studies are needed to optimize treatment protocols.
2026-04-03 | Abstract 2263: Microenvironmental rewiring in giant cell tumor of bone: Stromal lineage hierarchy, immune diversion, and novel osteoclastogenic and angiogenic circuits.
Abstract Giant cell tumor of bone (GCTB) is a locally aggressive osteolytic neoplasm characterized by neoplastic stromal cells and abundant osteoclast-like giant cells, yet the microenvironmental architecture and regulatory networks that sustain tumor progression remain incompletely understood. Here, we performed integrated single-cell RNA sequencing and spatial transcriptomics on six treatment-naïve primary GCTB specimens to generate a high-resolution atlas of stromal, immune, myeloid, osteoclastic and vascular compartments. We identify a structured mesenchymal hierarchy linking pericytes, osteoblast precursors and tumor stromal cells through a continuous transcriptional trajectory, providing evidence that the neoplastic stromal population arises from, or co-evolves with, osteogenic and perivascular lineages. Tumor cells display marked inter- and intra-patient heterogeneity, characterized by discrete EMT-, coagulation-, myogenesis- and androgen-responsive subclusters, indicating diverse functional specializations within the stromal tumor compartment.Despite substantial cytotoxic T-cell infiltration across all patients, ligand-receptor inference revealed that effector immune signals—including CCL and PARs pathways—are preferentially directed toward osteoclast-like giant cells rather than tumor cells, suggesting an “immune diversion” or “immune sink” mechanism that may blunt anti-tumor immunity despite preserved T-cell functional states. Beyond confirming the canonical tumor-derived RANKL engagement of giant cells, we uncover two additional regulatory circuits: (i) a tumor-specific CHAD-ITGA2 signaling axis, with ITGA2 expression uniquely restricted to giant cells, implicating a selective osteoclastogenic mechanism with therapeutic potential; and (ii) a multisource CSF1/IL34-CSF1R network arising from tumor cells, osteoblast precursors and pericytes, cooperatively shaping myeloid recruitment and giant-cell formation, further supporting a shared stromal origin among these lineages.Finally, we identify a tumor-exclusive APELA-APLNR (APJ) angiogenic axis linking ligand production strictly in tumor cells to receptor expression exclusively in endothelial cells. Spatial transcriptomics confirmed that APELA is enriched within RANKL-high tumor niches, revealing a spatially confined angiogenic microdomain functionally distinct from the broadly distributed VEGF pathway.Together, this atlas defines the cellular logic and intercellular circuitry underlying GCTB progression and identifies multiple stromal, immune, osteoclastogenic and vascular vulnerabilities—including the CHAD-ITGA2 and APELA-APLNR axes—that may guide therapeutic strategies beyond RANKL inhibition. Citation Format: Chao Zhang, Jilong Yang, Xiangchun Li, Kexin Chen, Hongru Shen, Zhichao Liao. Microenvironmental rewiring in giant cell tumor of bone: Stromal lineage hierarchy, immune diversion, and novel osteoclastogenic and angiogenic circuits [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2263.
2026-03-06 | The single cell transcriptomic landscape of recurrent giant cell tumor of bone following neoadjuvant denosumab therapy.
Denosumab (DMAb) is widely used as a neoadjuvant therapy to downstage giant cell tumor of bone (GCTB). However, increasing evidence demonstrates that neoadjuvant DMAb may increase the local recurrence (LR) risk following curettage of GCTB. It remains unclear about the potential mechanisms for neoadjuvant DMAb-associated LR of GCTB. Here, we perform single-cell RNA sequencing on untreated primary GCTB, neoadjuvant DMAb-treated primary GCTB, and relapsed GCTB following discontinuation of DMAb after curettage. A total of 33,440 cells are obtained. Osteoclast-like giant cells nearly disappear in primary GCTB after neoadjuvant DMAb treatment, but rebound following DMAb discontinuation in recurrent GCTB. Neoadjuvant DMAb therapy induces the transformation of TNFSF11 (RANKL)-positive neoplastic cells into SPP1 (osteopontin)-positive and CA2-positive neoplastic cells. Neoadjuvant DMAb therapy induces a durable intratumoral immunosuppressive environment, characterized by an increased frequency of regulatory T cells and decreased levels of cytotoxic CD8+ T cells and natural killer T (NKT) cells. In addition, DMAb-induced differentiation of monocytes to Trem2+ macrophages provides a favorable microenvironment that facilitates tumor relapse. CSF1R inhibitor can inhibit the tumor growth of recurrent GCTB. Targeting CSF1R and alleviating T cell exhaustion may provide therapeutic insights for the management of relapsed GCTB following DMAb discontinuation.
proteins
2025-08-06 | An Innovative Reconstruction Technique for Proximal Tibia Grade 3 Giant Cell Tumor: The Sky Roof Reconstruction Approach
Giant cell tumor (GCT) of the bone, although benign, demonstrates local aggressiveness, a potential for recurrence, and, in rare instances, malignant transformation. Functional preservation is crucial in cases involving the articular surface, often utilizing the Sandwich Technique. We propose an enhanced reconstruction method using the inner table of the iliac crest in a reverse fashion, offering a more anatomically contoured proximal tibial plateau and reducing donor site morbidity compared to tricortical iliac crest grafting. This technique ensures that the marrow and cancellous bone facing the articular cartilage provide essential nourishment for articular cartilage, preventing early joint arthritis.
2024-02-12 | Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src
Abstract Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1 , Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.
2024-01-30 | Interferons as Neoadjuvant Chemotherapy for Giant Cell Tumor: A Hospital-Based Prospective Pilot Study
Abstract Introduction Neoadjuvant chemotherapy is now considered an effective way to treat Campanacci grade 2 and 3 giant cell tumors (GCTs). Assessment of these drugs is essential clinically, radiologically, and pathologically. This study analyzes the early results of angiogenesis inhibitors (interferons) in the aggressive GCT of bone. Methodology A prospective pilot study was conducted from January 2021 to July 2022 including eight biopsy-proven GCT patients subjected to interferon therapy. Radiological assessment was done with changes on plain radiograph, computerized tomography scan, and magnetic resonance imaging. Histopathological examination was done by changes in the biopsy and resected segment. Results Out of the eight patients included in the study, 26% (n = 3) were males and 62% (n = 5) were females, with mean age of the patients being 24.6 ± 8.48 years (range: 22–38). There was significant reduction of the size of swelling (p-value: 0.049), significant reduction in Visual Analog Scale score (p-value: 0.011), significant decrease in swelling size on radiograph (p-value: 0.012), significant marginal sclerosis (p-value: 0.001), significant neocortex formation on radiographs (p-value: 0.001), significant result in and osteoid formation (p-value: 0.001) on histology. Whereas Campanacci grade on plain radiographs, number of viable cells, and number of viable stromal cell were not statistically different in comparison with pretherapy and posttherapy status. Conclusion Interferon therapy in a GCT has potential beneficiary effect in terms of clinical, radiological, and pathological outcomes. It might prove to be an effective alternative to standard neoadjuvant chemotherapy in the management of aggressive GCT of bones. Level of Evidence III.
2024-01-15 | Human Chorionic Gonadotropin Regulates the Smad Signaling Pathway by Antagonizing TGF-β in Giant Cell Tumor of Bone.
Giant cell tumor of bone (GCTB) is a locally aggressive bone tumour aggravated by stromal cell proliferation and metastasis. We investigated the mechanism of action of human chorionic gonadotropin (HCG) in mediating GCTB proliferation and invasion. The expression of HCG was quantified using quantitative real-time PCR. After the primary stromal cells were isolated and identified, the function of HCG in GCTB was estimated using the cell counting kit-8, flow cytometry, scratch experiment, transwell assay, Western blot, and immunofluorescence. Moreover, the mechanism of HCG was assessed through western blotting. HCG expression was decreased in clinical tissue samples from patients with GCTB. We validated that HCG repressed stromal cell proliferation, migration, invasion, autophagy, and epithelial- mesenchymal transition (EMT) and promoted cell apoptosis in GCTB. We also verified that HCG repressed the autophagy and EMT of stromal cells through the Smad signaling axis in GCTB. HCG inhibited the transduction of the Smad signaling pathway by restraining the binding of the TGF-β II receptor to ligand Activin A. HCG restrained the Smad signaling pathway by antagonizing TGF-β signaling in GCTB. HCG may serve as a useful patent to treat GCTB.
2021-05-21 | Incidence, Management, and Outcomes of Spinal Giant Cell Tumor of Bone in Adult Patients: A National Cancer Database Analysis.
Giant cell tumors (GCTs) constitute 5% of all primary bone tumors with spinal GCTs (SGCTs) accounting for 2%-15% of all GCTs. The standard of care for SGCT has been maximal surgical resection. However, many adjuvant therapies have been used owing to the difficulty in achieving gross total resection combined with the high local recurrence rate. The purpose of the present study was to analyze the incidence, management, and outcomes of SGCT. Patients with diagnosis codes specific for SGCT were queried from the National Cancer Database from 2004 to 2016. The outcomes were investigated using Cox univariate and multivariate regression analyses, and survival curves were generated for comparative visualization. The search criteria identified 92 patients in the NCDB dataset from 2004 to 2016 with a diagnosis of SGCT. Of the 92 patients, 64.1% had undergone surgical intervention, 24.8% had received radiotherapy, and 15.2% had received immunotherapy. Univariate analysis revealed that age ≥55 years and tumor location in the sacrum/coccyx were associated with worsened overall survival (OS) and that surgical resection was associated with improved OS. On multivariate analysis, age 55-64 years was associated with worsened OS, and radical surgical resection was associated with improved OS. The survival analysis revealed improved OS with surgery but not with radiotherapy, chemotherapy, or immunotherapy. SGCT is a rare primary bone tumor of the vertebral column. The standard of care has been surgical resection with the goal of gross total resection; however, adjuvant therapies have often been used. Our study found that surgical resection significantly improved OS and that immunotherapy neared significance in improving OS.
antibodies
2026-08-14 | Efficacy of Neoadjuvant Denosumab on Tumor Recurrence, Ossification, and Surgical Outcomes in Patients With Grade III Giant Cell Tumor of Bone: A Prospective, Non-Randomized Comparative Interventional Study.
Giant cell tumor of bone (GCTB) is a rare, locally aggressive osteolytic neoplasm associated with a substantial risk of local recurrence and challenging surgical management. Denosumab, a monoclonal antibody, has emerged as a promising therapeutic option. This study evaluates the efficacy of denosumab as a neoadjuvant therapy in patients with Grade III GCTB, with particular emphasis on tumor recurrence, ossification, and surgical outcomes. In this prospective, non-randomized comparative interventional study, 34 adults with histologically confirmed Campanacci Grade III GCTB were enrolled and prospectively followed. Sixteen patients received neoadjuvant denosumab and 18 contemporaneous patients underwent surgery without neoadjuvant denosumab. Treatment allocation was based on routine clinical decision-making and patient-specific factors rather than randomization. During the 18-month follow-up period, local recurrence occurred in 2 of 16 patients (12.5%) in the denosumab intervention group and in 8 of 18 patients (44.4%) in the comparison group (p = 0.063). Radiological ossification was observed in all patients in the denosumab group and in none of the patients in the comparison group. Curettage and cementation were performed in 14 patients (87.5%) in the intervention group and 12 patients (66.7%) in the comparison group; this difference was not statistically significant (p = 0.233). Qualitative histopathological assessment of available specimens from denosumab-treated patients demonstrated marked depletion or disappearance of osteoclast-like giant cells, accompanied by treatment-related changes including new bone formation, fibrosis, and hemorrhage. In this study, neoadjuvant denosumab was associated with complete radiological ossification, qualitative histopathological changes characterized by marked depletion of osteoclast-like giant cells, and numerically lower observed local recurrence and greater use of curettage and cementation, although the latter two between-group differences were not statistically significant.
2026-08-14 | Extensive Giant Cell Tumor Involving Entire Tibia with Talar Extension and Pulmonary Metastases: Successful Limb Preservation with Denosumab and Angioembolization.
Giant cell tumor of bone (GCTB) is a benign but locally aggressive neoplasm with a recognized propensity for recurrence and occasional pulmonary metastasis. Diffuse involvement of an entire long bone is exceptionally rare. A 29-year-old female with four previous surgeries for recurrent distal tibial giant cell tumor presented with extensive involvement of the entire tibia, talar extension, and pulmonary metastases. Histopathology and H3.3G34W immunostaining confirmed the diagnosis. Limb salvage reconstruction was not feasible and amputation was declined. Selective angioembolization followed by denosumab 120 mg monthly for 6 months resulted in significant clinical improvement and disease stabilization. At 24 months, the patient remained independently ambulatory with stable local and pulmonary disease. Combined angioembolization and denosumab may provide durable disease control and limb preservation in selected patients with extensive unresectable GCTB.
2026-07-01 | Indication-specific use of Denosumab in Giant Cell Tumour of Bone: A retrospective cohort study.
Giant Cell Tumours of Bone (GCTB) are locally aggressive, benign bone tumours. Denosumab was initially introduced as a neoadjuvant therapy to facilitate curettage but is now also used prior to en-bloc resection, as definitive treatment for unresectable disease, and as long-term treatment for recurrent or metastatic disease. Evidence regarding indication-specific outcomes remains limited. This study evaluated contemporary Denosumab use according to treatment intent, focusing on treatment duration, recurrence patterns, and long-term administration. A retrospective review was conducted of all GCTB patients treated with Denosumab at the Royal Orthopaedic Hospital, Birmingham, between 2010 and 2023. Patients were categorized according to treatment intent: 1) Short-course Neoadjuvant Denosumab (SCND), 2) Long-course Neoadjuvant Denosumab (LCND), 3) Definitive Denosumab for unresectable disease, and 4) Long-term Denosumab following local or distant recurrence. The study included 155 patients. Twenty-eight patients (18%) received SCND for median 15 weeks (IQR 11-20), local recurrence occurring in 13 patients (46%). Fifty-two patients (34%) received LCND for median 22 weeks (IQR 13-54), local recurrence occurring in 6 patients (12%). Forty-two patients (27%) received definitive Denosumab for median 123 weeks (IQR 83-182), while 33 patients (21%) received long-term Denosumab following recurrence for median 123 weeks (IQR 29-247). Dose de-escalation was frequently feasible in patients with sustained disease control, whereas adverse events were primarily associated with prolonged treatment exposure. This study demonstrates that Denosumab is used across several distinct clinical indications in GCTB. High recurrence rates were observed following short-course neoadjuvant treatment prior to curettage, whereas prolonged disease control was frequently achieved in selected patients receiving definitive or long-term Denosumab. A preliminary clinical framework for indication-specific Denosumab use is proposed and warrants prospective validation.
2026-07-01 | Giant Cell Tumor of the Cervical Axis Treated With Anterior-Posterior Surgery and Denosumab: A Ten-year Follow-up Case Report.
Giant cell tumor of the bone (GCTB) is a benign but locally aggressive neoplasm that rarely involves the cervical spine, accounting for approximately 1-4% of all primary bone tumors. The cervical axis (C2) is an exceptionally rare site, presenting unique surgical challenges due to its complex anatomy and proximity to vital neurovascular structures. Denosumab, a monoclonal antibody targeting RANKL, has emerged as an important adjuvant therapy for unresectable or surgically challenging GCTB. Long-term outcomes of combined surgical resection and denosumab therapy in cervical spine GCTB remain poorly documented. We report the case of a 16-year-old Japanese male with a history of malignant lymphoma who presented with neck pain and a lytic lesion of the C2 vertebral body. Imaging revealed a 3.5×2.8×2.5 cm expansile lesion with extraosseous extension and encasement of the right vertebral artery. Biopsy confirmed GCTB. The patient received preoperative denosumab (120 mg on days 1, 8, and 15 of month 1, then monthly for 7 additional months) followed by right vertebral artery embolization. A two-stage anterior-posterior surgical resection was performed via mandibular osteotomy, with C1 lateral mass and C3 pedicle screw fixation and tricortical iliac crest autograft reconstruction. Postoperative denosumab (120 mg monthly) was continued for 16 months. At 10-year follow-up, the patient remains recurrence-free with solid bony fusion, no neurological deficits, and excellent functional outcomes (VAS 0/10, JOA score 17/17). This case demonstrates that combined anterior-posterior surgical resection with perioperative denosumab therapy can achieve excellent long-term tumor control and functional outcomes in C2 GCTB. Extended preoperative denosumab facilitated tumor ossification and surgical resection, while postoperative denosumab may reduce recurrence risk. Long-term surveillance remains essential given the variable recurrence patterns in spinal GCTB.
2026-05-25 | Metachronous multicentric giant cell tumor of bone with pulmonary metastases: a case report with 20-year follow-up.
Giant cell tumor of bone (GCTB) is typically a solitary lesion, with multicentric metachronous GCTB (MGCTB) accompanied by pulmonary metastasis being exceedingly rare and posing notable management challenges. A case of MGCTB with 20 years follow up at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology is reported, and relevant literatures are reviewed. This report details a 38-year-old male with MGCTB and pulmonary metastases, followed for over 20 years since his initial treatment in 2005. Despite multiple surgical interventions, including curettage, resection, and eventual amputation, the disease progressed with new osteolytic lesions emerging years later. Systemic therapy with denosumab, initiated in 2017, achieved sustained disease stabilization. Following a treatment interruption during the COVID-19 pandemic, denosumab was resumed in 2021 and effectively controlled systemic lesions; however, a persistently progressing rib lesion necessitated wide en bloc resection in 2022. To date, the patient continues on denosumab with well-controlled disease and no evidence of progression, illustrating its critical role in achieving long-term control in this rare, aggressive GCTB variant. MGCTB is extremely rare. This case underscores the importance of continuous systemic therapy in managing MGCTB, even in the context of surgical interventions.
other
2026-03-24 | Giant cell tumor of bone inhibits osteoblastogenesis via WNT5B.
Giant cell tumor of bone (GCTB) induces overproduction of bone-resorbing osteoclasts through receptor activator of nuclear factor kappa B ligand (RANKL), leading to bone resorption and destruction. Consequently, denosumab, a neutralizing antibody against RANKL (a cytokine essential for osteoclast induction), is used to treat patients with GCTB. However, the activity of bone formation in GCTB remains poorly understood. Here, we show that GCTB antagonizes bone formation by expressing WNT5B, which inhibits bone formation. Co-culture of NCC-GCTB1-C1 (GCTB1s), a human GCTB cell line, with human adipose-derived stem cells (ADSCs) was performed with osteoblast induction medium. To identify the inhibitors of osteoblast differentiation, we reanalyzed the single-cell RNA sequencing data that was previously published. In addition, we performed spatial transcriptome analysis (Visium) against the section of paraffin block of GCTB. The targeted protein was knocked out using CRISPR/Cas9 and co-culture was performed. Co-culture of GCTB1s with ADSCs significantly inhibited mineralization of ADSCs. Reanalysis of single-cell RNA sequencing data indicated that GCTB tumors express WNT5B, and we observed that GCTB1s express WNT5B. We then knocked out WNT5B in GCTB1s using CRISPR/Cas9 and co-cultured them with ADSCs and observed significant rescue of mineralization in ADSCs relative to ADSCs cultured with GCTB1s expressing WNT5B. We also show that ADSC supernatants induce mineralization of GCTB1s. These studies indicate that GCTB not only induces osteoclasts, but also possesses activity that inhibits bone formation.
2024-08-15 | H3.3-G34W in giant cell tumor of bone functionally aligns with the exon choice repressor hnRNPA1L2.
RNA processing is an essential post-transcriptional phenomenon that provides the necessary complexity of transcript diversity prior to translation. Aberrations in this process could contribute to tumourigenesis, and we have previously reported increased splicing alterations in giant cell tumor of bone (GCTB), which carries mutations in the histone variant H3.3 encoding glycine 34 substituted for tryptophan (H3.3-G34W). G34W interacts with several splicing factors, most notably the trans-acting splicing factor hnRNPA1L2. To gain a deeper understanding of RNA processing in GCTB and isogenic HeLa cells with H3.3-G34W, we generated RNA-immunoprecipitation sequencing data from hnRNPA1L2 and H3.3-G34W associated RNAs, which showed that 80% overlapped across genic regions and were frequently annotated as E2F transcription factor binding sites. Splicing aberrations in both GCTB and HeLa cells with H3.3-G34W were significantly enriched for known hnRNPA1L2 binding motifs (p value < 0.01). This splicing aberration differed from hnRNPA1L2 knockouts, which showed alterations independent of H3.3-G34W. Of functional significance, hnRNPA1L2 was redistributed to closely match the H3.3 pattern, likely driven by G34W, and to loci not occupied in normal parental cells. Taken together, our data reveal a functional overlap between hnRNPA1L2 and H3.3-G34W with likely significant consequences for RNA processing during GCTB pathogenesis. This provides novel opportunities for therapeutic intervention in future modus operandi.
2024-02-01 | Association of miRNA and Bone Tumors: Future Therapeutic Inroads.
Small endogenous non-coding RNA molecules known as micro-ribonucleic acids (miRNAs) control post-transcriptional gene regulation. A change in miRNA expression is related to various diseases, including bone tumors. Benign bone tumors are categorized based on matrix production and predominant cell type. Osteochondromas and giant cell tumors are among the most common bone tumors. Interestingly, miRNAs can function as either tumor suppressor genes or oncogenes, thereby determining the fate of a tumor. In the present review, we discuss various bone tumors with regard to their prognosis, pathogenesis, and diagnosis. The association between miRNAs and bone tumors, such as osteosarcoma, Ewing's sarcoma, chondrosarcoma, and giant-cell tumors, is also discussed. Moreover, miRNA may play an important role in tumor proliferation, growth, and metastasis. Knowledge of the dysregulation, amplification, and deletion of miRNA can be beneficial for the treatment of various bone cancers. The miRNAs could be beneficial for prognosis, treatment, future drug design, and treatment of resistant cases of bone cancer.
2021-07-09 | microRNAs and bone tumours: Role of tiny molecules in the development and progression of chondrosarcoma, of giant cell tumour of bone and of Ewing's sarcoma.
The increasing interest on microRNAs (miRNAs), small non-coding RNA molecules containing about 22 nucleotides, about their biological functions led researchers to discover that they are actively involved in several biological processes. In the last decades, miRNAs become one of the most topic of cancer research. miRNAs, thanks to their function, are the perfect molecules to modulate multiple signaling pathways and gene expression in cancer, with the consequent capacity to modulate cancerous processes, such as cellular proliferation, invasion, metastasis and chemoresistance in various tumours. In the last years, several studies have demonstrated the role of miRNAs in their pathophysiology, but little we know about the underlying mechanism that lead to bone tumours like chondrosarcoma (COS), giant cell tumour of bone (GCTB) and Ewing sarcoma (EWS) to still be highly aggressive and resistant tumours. An exploration of the role of miRNAs in the biology of them will permit to researchers to find new molecular mechanisms that can be used to develop new and more effective therapies against these bone tumours. Here we present a comprehensive study of the latest discoveries which have been performed in relation to the role of miRNAs in the neoplastic processes which characterize COS, EWS and GCTB, demonstrating how these tiny molecules can act as tumour promoters or as tumour suppressors and how they can be used for improving therapeutic approaches.
2020-03-10 | Expression profiles of miRNAs in giant cell tumor of bone showed miR‐187‐5p and miR‐1323 can regulate biological functions through inhibiting FRS2
Abstract Background Giant cell tumor of bone (GCTB) is considered to be a kind of borderline tumor, which has a tendency to recur and translocate. MicroRNAs are one type of small noncoding RNA, which can inhibit the translation of targeted mRNA through RNA‐induced silencing complex. Methods Microarray was conducted on three groups of tumor tissues and normal tissues from patients with GCTB, and results showed different expression profiles of miRNAs with Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis. The functions of miR‐187‐5p and miR‐1323, which were highly expressed in GCTB, were examined by 5‐ethynyl‐2′‐deoxyuridine (EDU), transwell, and CCK8 assays. RNAhybrid et al. ( RNA prediction softwares) predicted that the two microRNAs targeted fibroblast growth factor receptor substrate 2 (FRS2), which was verified by luciferase assay and rescue experiments. Results miR‐187‐5p and miR‐1323 were highly expressed in tumor tissues. They can jointly regulate the biological functions of GCTB in vitro. Luciferase assay confirmed that the two microRNAs can bind to the 3′ untranslated regions (UTR) of mRNA of FRS2. And, rescue experiments verified the relationships between the two microRNAs and FRS2. Conclusion There were some different‐expressed microRNAs between GCTB and normal tissues. miR‐187‐5p and miR‐1323 can regulate the biological functions of GCTB through influencing the expression of FRS2.
cell therapies
2026-08-07 | Intralesional resection and autologous fibular graft reconstruction for a giant cell tumor of the fourth metacarpal with a secondary aneurysmal bone cyst: a case report
Introduction and importance: Giant cell tumor (GCT) of bone rarely involves the metacarpal bones. Secondary aneurysmal bone cyst (ABC) changes arising in association with GCT create distinct diagnostic and therapeutic challenges in this uncommon skeletal location. Case presentation: A 21-year-old right-hand-dominant female presented with progressive right fourth metacarpal pain and swelling following minor trauma. Radiographs and magnetic resonance imaging (MRI) demonstrated an expansile osteolytic lesion with cortical thinning and internal fluid–fluid levels suggesting GCT with secondary ABC changes. Preoperative chest radiography showed no evidence of pulmonary metastasis. Intralesional resection was performed while preserving the metacarpal head articular surface. Biological reconstruction was achieved using a non-vascularized autologous fibular graft stabilized with Kirschner wires. Histopathological examination confirmed GCT associated with secondary ABC changes and excluded telangiectatic osteosarcoma. At the 6-month follow-up, the patient demonstrated satisfactory graft incorporation, excellent hand function, and no evidence of local recurrence or pulmonary metastasis. Clinical discussion: Hand GCTs exhibit more aggressive behavior and higher recurrence rates than those in conventional skeletal locations. Differentiating secondary ABC from primary ABC and from telangiectatic osteosarcoma is essential, as treatment strategies and oncological implications differ significantly. Conclusion: Intralesional resection followed by biological reconstruction using a non-vascularized autologous fibular graft preserves hand function while achieving satisfactory early local disease control in selected patients.
2026-07-10 | Short-term Functional Outcomes of Shoulder Girdle Limb Salvage in Primary Bone Tumors: A 2-year Follow-up Study.
The shoulder girdle, encompassing the proximal humerus, scapula, lateral third of the clavicle, and surrounding soft tissues, is the third most frequent site for bone tumors. The proximal humerus is the most commonly affected area, followed by the scapula and clavicle. Managing malignant or aggressive benign bone tumors in this region is particularly challenging due to the proximity to vital neurovascular structures and the need to maintain both stability and dexterity in the shoulder. While traditional treatment often involved extensive resections, contemporary limb salvage techniques focus on preserving function while ensuring effective tumor control. This prospective study included 18 patients who underwent various limb salvage procedures at the Department of Orthopaedics, Vydehi Institute of Medical Sciences and Research Centre in Bengaluru between 2012 and 2019, with a minimum follow-up of 2 years. Diagnosis and staging were performed using imaging modalities and core needle biopsies, with musculoskeletal tumors staged according to the Enneking System. Functional outcomes were assessed using the Musculoskeletal Tumor Society Rating Scale (MSTS). Surgical techniques varied and included endoprosthetic reconstruction, arthrodesis with fibular grafting and plating, and plate fixation with primary shortening. Among the 18 patients, the majority (61%) had giant cell tumors, followed by aneurysmal bone cysts (17%), chondrosarcoma (11%), and osteosarcoma (11%). Functional outcomes, as measured by the MSTS, showed a 75% satisfactory rate. The study population was composed of 55.56% males and 44.44% females. Key parameters evaluated included pain, functional activity, hand positioning, dexterity, lifting ability, and emotional acceptance. Limb salvage surgery for primary bone tumors of the shoulder girdle offers favorable functional outcomes and represents a viable alternative to amputation. Modern reconstruction techniques, such as endoprosthetic reconstruction and fibular grafting with plating, achieve satisfactory results in both function and appearance. The MSTS scoring system is an effective tool for assessing postoperative functional status, and there is a growing preference for less aggressive surgical techniques that preserve limb function while ensuring tumor control.
2026-06-17 | Optimal management of giant cell tumor in the tibial plateau: A case report on curettage and cement reinforcement.
Giant cell tumor of bone (GCTB) is a benign yet locally aggressive neoplasm that commonly arises in the epiphyseal metaphyseal region of long bones, particularly around the knee, where management is challenged by the need to achieve complete tumor excision while preserving joint function in young, active individuals. We describe a 26-year-old female who presented with acute left knee pain and mechanical locking after squatting during exercise. Imaging demonstrated a well-defined 1.7 × 1.7 × 1.7 cm eccentric lesion in the posterior medial tibial plateau with minimal cortical breakthrough and surrounding marrow edema, and CT guided biopsy confirmed the diagnosis of GCTB. She underwent surgery through a posterior Löbbenhofer approach, including meticulous curettage, high speed burring, and phenol application. To shield the articular cartilage from the thermal effects of PMMA cement and avoid long term subchondral stiffness, a protective layer of autologous morselized bone graft was interposed between the cement and the joint surface. Recovery was uneventful, and this single-stage technique provided definitive management with no need for further surgery, ensuring structural support while minimizing recurrence risk. This case highlights the value of combining extended curettage with a graft cement interface to optimize joint preservation in periarticular GCTB and underscores the need for future studies evaluating long term radiological and functional outcomes of such hybrid reconstructions.
2026-06-11 | A Rare Case of Giant Cell Tumor of the First Metatarsal: En Bloc Resection and Fibular Autograft Reconstruction.
Giant cell tumors (GCTs) of bone are benign but locally aggressive neoplasms that predominantly involve the epiphyseal regions of long bones, with the first metatarsal being an exceptionally rare site of involvement. This case report describes the clinical presentation, diagnostic evaluation, surgical management, and functional outcomes of a rare GCT involving the first metatarsal bone. A 54-year-old female presented with a 5-month history of progressive pain and swelling of the right foot localized over the first metatarsal region. Clinical examination revealed a firm, tender, bony expansion measuring approximately 3 × 5 × 3 cm. Radiological investigations, including plain radiography, multiplanar MRI and CT imaging confirmed an osteolytic, expansile lesion suggestive of GCT. En bloc resection of the tumor-bearing segment was performed with reconstruction using non-vascularized fibular autograft fixation with K-wires. Histopathological examination confirmed the diagnosis of GCT of bone. The patient achieved complete surgical resection with excellent functional recovery at 12-month follow-up. The fibular autograft demonstrated satisfactory integration without evidence of recurrence or significant complications. Functional outcome scores improved significantly, and the patient resumed normal weight-bearing activities. Although rare, GCT of the first metatarsal should be considered in the differential diagnosis of expansile osteolytic lesions in the foot. En bloc resection with non-vascularized fibular autograft reconstruction provides oncologically sound treatment with acceptable functional outcomes and minimal recurrence rates. This case underscores the importance of multimodal imaging, histopathological confirmation, and meticulous surgical planning in managing this challenging presentation.
2026-06-11 | Giant Cell Tumor of the Metacarpal Treated with Non-Vascularized Bone Graft: A Case Report.
Giant cell tumor (GCT) of bone is a benign but locally aggressive neoplasm, most commonly affecting the epiphyseal region of long bones. Involvement of the hand bones is rare and is known to exhibit more aggressive behavior with higher recurrence rates compared to conventional sites. Optimal reconstruction following tumor excision in the hand remains challenging, as, along with the reconstruction of the bone defect, the function of the hand should also be addressed. A 19-year-old right-hand-dominant female presented with a progressively enlarging, painful swelling over the dorsum of the right hand. Radiological evaluation revealed an expansile, lytic lesion involving the ring finger metacarpal with cortical breach. Magnetic resonance imaging showed an aggressive lesion with soft-tissue involvement. Histopathological examination confirmed the diagnosis of GCT of bone. The patient underwent wide excision of the tumor followed by reconstruction using a non-vascularized autologous cortical bone graft from the ulna. GCT of the metacarpal is rare and requires aggressive surgical management due to its high recurrence potential. Non-vascularized ulnar bone graft provides a reliable, simple, and effective reconstructive option following tumor excision.
small molecules
2026-07-10 | A Rare Case of Giant Cell tumor of Bone in Distal Tibia.
Giant cell tumors of bone commonly seen in the distal femur, proximal tibia and distal radius and are seen in the age group of 20-40 years with female preponderance. Being close to the joint, the management is formidable, and there are no clinical, radiological or histological parameters to predict chances of recurrence or metastasis. Here, we present a rare case of giant cell tumor of the distal tibia treated successfully with no recurrence at the end of 4 years. A 33-year-old female presented with complaints of pain, swelling and decreased range of motion (ROM) at the left ankle joint for 6 weeks. On examination, we observed swelling and tenderness on left ankle joint with decreased ROM. X-rays and computed tomography revealed a well-defined expansile osteolytic lesion in the distal epiphysio-metaphyseal region of the left tibia without breach in the tibial cortex or ankle joint. Surgery by extensive curettage, adjuvants, cementation and prophylactic fixation was performed. Oral alendronate was started and continued for 24 months after surgery. The patient at 4-year follow-up is doing well, walking without pain, able to squat, having full ROM of the ankle joint with no signs of recurrence.
2026-07-01 | ICG-based NIR fluorescence imaging can help to detect residual giant cell tumor of bone after intralesional curettage: Results of two-year follow-up.
Identification of clinical occult tumor residuals is crucial during giant cell tumor (GCT) intralesional curettage. This study investigated the capacity of indocyanine green (ICG) fluorescence imaging to detect tumor residual during intralesional curettage of GCT. Clinical data of 20 patients with GCT who received ICG near-infrared (NIR) fluorescence-assisted intralesional curettage with a minimal two-year follow-up in our institute were reviewed. Tumors were initially curetted under white light with naked eyes. Then, wounds were scanned to detect fluorescence residuals. Biopsies were conducted on the sites with fluorescence positivity or negativity. The fluorescence intensity (FI) of biopsied samples were determined using standardized process, and samples were sent for pathological examination. All the tumors were successfully stained (100%). One patient (5%) experienced a local recurrence. The overall accuracy of ICG fluorescence in detecting tumor residuals (true positivity and true negativity) was 68%. The false positive rate and false negative rate were 38% and 21%, respectively. Fluorescence-positive samples showed a significantly higher rate of pathological positivity than negative samples (P = 0.001). The meanFI and maxFI of samples with pathological positivity were significantly higher than those with pathological negativity (P value was 0.001 and 0.002, respectively). The AUCROC values for meanFI and maxFI predicting pathological results were 0.713 and 0.719, respectively. ICG-based NIR fluorescence imaging can detect residual GCT after intralesional curettage, and can be used as a supplement to extended curettage to reduce recurrence. The FI is positively related to pathological results. However, false signals may occur. Efforts to increase accuracy and confirm its clinical benefits in preventing recurrence are still needed.
2026-06-08 | A Review of Endovascular Techniques as Therapy for Inoperable Giant Cell Bone Tumors of the Sacrum, Pelvis, and Spine
Abstract Giant cell tumor (GCT) of bone is a benign but locally aggressive neoplasm. Lesions in the sacrum, pelvis, and spine present surgical challenges due to complex anatomy. Selective arterial embolization (SAE) is a minimally invasive treatment option for inoperable GCTs. A narrative review of PubMed and Embase (1976–2024) identified studies that included patients with biopsy-proven GCTs of the sacrum, pelvis, or spine treated with SAE. Inclusion required non-surgical candidacy, treatment with SAE alone, or SAE with denosumab and/or radiotherapy. Studies involving GCTs of the extremities, surgical resection, or preoperative embolization were excluded. Outcomes that were assessed included clinical and radiographic response, recurrence, and complications. Among 70 patients, SAE alone showed 86% (25/29) clinical and 79% (23/29) radiographic response rates. SAE with radiotherapy showed a higher clinical and radiographic response than SAE with denosumab (83% clinical and 65% radiographic versus 39% clinical and 50% radiographic). Recurrence and metastasis varied across groups. SAE is an effective therapy for inoperable GCTs of the axial skeleton. Further studies are needed to optimize treatment protocols.
2026-04-03 | Abstract 2263: Microenvironmental rewiring in giant cell tumor of bone: Stromal lineage hierarchy, immune diversion, and novel osteoclastogenic and angiogenic circuits.
Abstract Giant cell tumor of bone (GCTB) is a locally aggressive osteolytic neoplasm characterized by neoplastic stromal cells and abundant osteoclast-like giant cells, yet the microenvironmental architecture and regulatory networks that sustain tumor progression remain incompletely understood. Here, we performed integrated single-cell RNA sequencing and spatial transcriptomics on six treatment-naïve primary GCTB specimens to generate a high-resolution atlas of stromal, immune, myeloid, osteoclastic and vascular compartments. We identify a structured mesenchymal hierarchy linking pericytes, osteoblast precursors and tumor stromal cells through a continuous transcriptional trajectory, providing evidence that the neoplastic stromal population arises from, or co-evolves with, osteogenic and perivascular lineages. Tumor cells display marked inter- and intra-patient heterogeneity, characterized by discrete EMT-, coagulation-, myogenesis- and androgen-responsive subclusters, indicating diverse functional specializations within the stromal tumor compartment.Despite substantial cytotoxic T-cell infiltration across all patients, ligand-receptor inference revealed that effector immune signals—including CCL and PARs pathways—are preferentially directed toward osteoclast-like giant cells rather than tumor cells, suggesting an “immune diversion” or “immune sink” mechanism that may blunt anti-tumor immunity despite preserved T-cell functional states. Beyond confirming the canonical tumor-derived RANKL engagement of giant cells, we uncover two additional regulatory circuits: (i) a tumor-specific CHAD-ITGA2 signaling axis, with ITGA2 expression uniquely restricted to giant cells, implicating a selective osteoclastogenic mechanism with therapeutic potential; and (ii) a multisource CSF1/IL34-CSF1R network arising from tumor cells, osteoblast precursors and pericytes, cooperatively shaping myeloid recruitment and giant-cell formation, further supporting a shared stromal origin among these lineages.Finally, we identify a tumor-exclusive APELA-APLNR (APJ) angiogenic axis linking ligand production strictly in tumor cells to receptor expression exclusively in endothelial cells. Spatial transcriptomics confirmed that APELA is enriched within RANKL-high tumor niches, revealing a spatially confined angiogenic microdomain functionally distinct from the broadly distributed VEGF pathway.Together, this atlas defines the cellular logic and intercellular circuitry underlying GCTB progression and identifies multiple stromal, immune, osteoclastogenic and vascular vulnerabilities—including the CHAD-ITGA2 and APELA-APLNR axes—that may guide therapeutic strategies beyond RANKL inhibition. Citation Format: Chao Zhang, Jilong Yang, Xiangchun Li, Kexin Chen, Hongru Shen, Zhichao Liao. Microenvironmental rewiring in giant cell tumor of bone: Stromal lineage hierarchy, immune diversion, and novel osteoclastogenic and angiogenic circuits [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2263.
2026-03-06 | The single cell transcriptomic landscape of recurrent giant cell tumor of bone following neoadjuvant denosumab therapy.
Denosumab (DMAb) is widely used as a neoadjuvant therapy to downstage giant cell tumor of bone (GCTB). However, increasing evidence demonstrates that neoadjuvant DMAb may increase the local recurrence (LR) risk following curettage of GCTB. It remains unclear about the potential mechanisms for neoadjuvant DMAb-associated LR of GCTB. Here, we perform single-cell RNA sequencing on untreated primary GCTB, neoadjuvant DMAb-treated primary GCTB, and relapsed GCTB following discontinuation of DMAb after curettage. A total of 33,440 cells are obtained. Osteoclast-like giant cells nearly disappear in primary GCTB after neoadjuvant DMAb treatment, but rebound following DMAb discontinuation in recurrent GCTB. Neoadjuvant DMAb therapy induces the transformation of TNFSF11 (RANKL)-positive neoplastic cells into SPP1 (osteopontin)-positive and CA2-positive neoplastic cells. Neoadjuvant DMAb therapy induces a durable intratumoral immunosuppressive environment, characterized by an increased frequency of regulatory T cells and decreased levels of cytotoxic CD8+ T cells and natural killer T (NKT) cells. In addition, DMAb-induced differentiation of monocytes to Trem2+ macrophages provides a favorable microenvironment that facilitates tumor relapse. CSF1R inhibitor can inhibit the tumor growth of recurrent GCTB. Targeting CSF1R and alleviating T cell exhaustion may provide therapeutic insights for the management of relapsed GCTB following DMAb discontinuation.
proteins
2025-08-06 | An Innovative Reconstruction Technique for Proximal Tibia Grade 3 Giant Cell Tumor: The Sky Roof Reconstruction Approach
Giant cell tumor (GCT) of the bone, although benign, demonstrates local aggressiveness, a potential for recurrence, and, in rare instances, malignant transformation. Functional preservation is crucial in cases involving the articular surface, often utilizing the Sandwich Technique. We propose an enhanced reconstruction method using the inner table of the iliac crest in a reverse fashion, offering a more anatomically contoured proximal tibial plateau and reducing donor site morbidity compared to tricortical iliac crest grafting. This technique ensures that the marrow and cancellous bone facing the articular cartilage provide essential nourishment for articular cartilage, preventing early joint arthritis.
2024-02-12 | Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src
Abstract Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1 , Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.
2024-01-30 | Interferons as Neoadjuvant Chemotherapy for Giant Cell Tumor: A Hospital-Based Prospective Pilot Study
Abstract Introduction Neoadjuvant chemotherapy is now considered an effective way to treat Campanacci grade 2 and 3 giant cell tumors (GCTs). Assessment of these drugs is essential clinically, radiologically, and pathologically. This study analyzes the early results of angiogenesis inhibitors (interferons) in the aggressive GCT of bone. Methodology A prospective pilot study was conducted from January 2021 to July 2022 including eight biopsy-proven GCT patients subjected to interferon therapy. Radiological assessment was done with changes on plain radiograph, computerized tomography scan, and magnetic resonance imaging. Histopathological examination was done by changes in the biopsy and resected segment. Results Out of the eight patients included in the study, 26% (n = 3) were males and 62% (n = 5) were females, with mean age of the patients being 24.6 ± 8.48 years (range: 22–38). There was significant reduction of the size of swelling (p-value: 0.049), significant reduction in Visual Analog Scale score (p-value: 0.011), significant decrease in swelling size on radiograph (p-value: 0.012), significant marginal sclerosis (p-value: 0.001), significant neocortex formation on radiographs (p-value: 0.001), significant result in and osteoid formation (p-value: 0.001) on histology. Whereas Campanacci grade on plain radiographs, number of viable cells, and number of viable stromal cell were not statistically different in comparison with pretherapy and posttherapy status. Conclusion Interferon therapy in a GCT has potential beneficiary effect in terms of clinical, radiological, and pathological outcomes. It might prove to be an effective alternative to standard neoadjuvant chemotherapy in the management of aggressive GCT of bones. Level of Evidence III.
2024-01-15 | Human Chorionic Gonadotropin Regulates the Smad Signaling Pathway by Antagonizing TGF-β in Giant Cell Tumor of Bone.
Giant cell tumor of bone (GCTB) is a locally aggressive bone tumour aggravated by stromal cell proliferation and metastasis. We investigated the mechanism of action of human chorionic gonadotropin (HCG) in mediating GCTB proliferation and invasion. The expression of HCG was quantified using quantitative real-time PCR. After the primary stromal cells were isolated and identified, the function of HCG in GCTB was estimated using the cell counting kit-8, flow cytometry, scratch experiment, transwell assay, Western blot, and immunofluorescence. Moreover, the mechanism of HCG was assessed through western blotting. HCG expression was decreased in clinical tissue samples from patients with GCTB. We validated that HCG repressed stromal cell proliferation, migration, invasion, autophagy, and epithelial- mesenchymal transition (EMT) and promoted cell apoptosis in GCTB. We also verified that HCG repressed the autophagy and EMT of stromal cells through the Smad signaling axis in GCTB. HCG inhibited the transduction of the Smad signaling pathway by restraining the binding of the TGF-β II receptor to ligand Activin A. HCG restrained the Smad signaling pathway by antagonizing TGF-β signaling in GCTB. HCG may serve as a useful patent to treat GCTB.
2021-05-21 | Incidence, Management, and Outcomes of Spinal Giant Cell Tumor of Bone in Adult Patients: A National Cancer Database Analysis.
Giant cell tumors (GCTs) constitute 5% of all primary bone tumors with spinal GCTs (SGCTs) accounting for 2%-15% of all GCTs. The standard of care for SGCT has been maximal surgical resection. However, many adjuvant therapies have been used owing to the difficulty in achieving gross total resection combined with the high local recurrence rate. The purpose of the present study was to analyze the incidence, management, and outcomes of SGCT. Patients with diagnosis codes specific for SGCT were queried from the National Cancer Database from 2004 to 2016. The outcomes were investigated using Cox univariate and multivariate regression analyses, and survival curves were generated for comparative visualization. The search criteria identified 92 patients in the NCDB dataset from 2004 to 2016 with a diagnosis of SGCT. Of the 92 patients, 64.1% had undergone surgical intervention, 24.8% had received radiotherapy, and 15.2% had received immunotherapy. Univariate analysis revealed that age ≥55 years and tumor location in the sacrum/coccyx were associated with worsened overall survival (OS) and that surgical resection was associated with improved OS. On multivariate analysis, age 55-64 years was associated with worsened OS, and radical surgical resection was associated with improved OS. The survival analysis revealed improved OS with surgery but not with radiotherapy, chemotherapy, or immunotherapy. SGCT is a rare primary bone tumor of the vertebral column. The standard of care has been surgical resection with the goal of gross total resection; however, adjuvant therapies have often been used. Our study found that surgical resection significantly improved OS and that immunotherapy neared significance in improving OS.
antibodies
2026-08-14 | Efficacy of Neoadjuvant Denosumab on Tumor Recurrence, Ossification, and Surgical Outcomes in Patients With Grade III Giant Cell Tumor of Bone: A Prospective, Non-Randomized Comparative Interventional Study.
Giant cell tumor of bone (GCTB) is a rare, locally aggressive osteolytic neoplasm associated with a substantial risk of local recurrence and challenging surgical management. Denosumab, a monoclonal antibody, has emerged as a promising therapeutic option. This study evaluates the efficacy of denosumab as a neoadjuvant therapy in patients with Grade III GCTB, with particular emphasis on tumor recurrence, ossification, and surgical outcomes. In this prospective, non-randomized comparative interventional study, 34 adults with histologically confirmed Campanacci Grade III GCTB were enrolled and prospectively followed. Sixteen patients received neoadjuvant denosumab and 18 contemporaneous patients underwent surgery without neoadjuvant denosumab. Treatment allocation was based on routine clinical decision-making and patient-specific factors rather than randomization. During the 18-month follow-up period, local recurrence occurred in 2 of 16 patients (12.5%) in the denosumab intervention group and in 8 of 18 patients (44.4%) in the comparison group (p = 0.063). Radiological ossification was observed in all patients in the denosumab group and in none of the patients in the comparison group. Curettage and cementation were performed in 14 patients (87.5%) in the intervention group and 12 patients (66.7%) in the comparison group; this difference was not statistically significant (p = 0.233). Qualitative histopathological assessment of available specimens from denosumab-treated patients demonstrated marked depletion or disappearance of osteoclast-like giant cells, accompanied by treatment-related changes including new bone formation, fibrosis, and hemorrhage. In this study, neoadjuvant denosumab was associated with complete radiological ossification, qualitative histopathological changes characterized by marked depletion of osteoclast-like giant cells, and numerically lower observed local recurrence and greater use of curettage and cementation, although the latter two between-group differences were not statistically significant.
2026-08-14 | Extensive Giant Cell Tumor Involving Entire Tibia with Talar Extension and Pulmonary Metastases: Successful Limb Preservation with Denosumab and Angioembolization.
Giant cell tumor of bone (GCTB) is a benign but locally aggressive neoplasm with a recognized propensity for recurrence and occasional pulmonary metastasis. Diffuse involvement of an entire long bone is exceptionally rare. A 29-year-old female with four previous surgeries for recurrent distal tibial giant cell tumor presented with extensive involvement of the entire tibia, talar extension, and pulmonary metastases. Histopathology and H3.3G34W immunostaining confirmed the diagnosis. Limb salvage reconstruction was not feasible and amputation was declined. Selective angioembolization followed by denosumab 120 mg monthly for 6 months resulted in significant clinical improvement and disease stabilization. At 24 months, the patient remained independently ambulatory with stable local and pulmonary disease. Combined angioembolization and denosumab may provide durable disease control and limb preservation in selected patients with extensive unresectable GCTB.
2026-07-01 | Indication-specific use of Denosumab in Giant Cell Tumour of Bone: A retrospective cohort study.
Giant Cell Tumours of Bone (GCTB) are locally aggressive, benign bone tumours. Denosumab was initially introduced as a neoadjuvant therapy to facilitate curettage but is now also used prior to en-bloc resection, as definitive treatment for unresectable disease, and as long-term treatment for recurrent or metastatic disease. Evidence regarding indication-specific outcomes remains limited. This study evaluated contemporary Denosumab use according to treatment intent, focusing on treatment duration, recurrence patterns, and long-term administration. A retrospective review was conducted of all GCTB patients treated with Denosumab at the Royal Orthopaedic Hospital, Birmingham, between 2010 and 2023. Patients were categorized according to treatment intent: 1) Short-course Neoadjuvant Denosumab (SCND), 2) Long-course Neoadjuvant Denosumab (LCND), 3) Definitive Denosumab for unresectable disease, and 4) Long-term Denosumab following local or distant recurrence. The study included 155 patients. Twenty-eight patients (18%) received SCND for median 15 weeks (IQR 11-20), local recurrence occurring in 13 patients (46%). Fifty-two patients (34%) received LCND for median 22 weeks (IQR 13-54), local recurrence occurring in 6 patients (12%). Forty-two patients (27%) received definitive Denosumab for median 123 weeks (IQR 83-182), while 33 patients (21%) received long-term Denosumab following recurrence for median 123 weeks (IQR 29-247). Dose de-escalation was frequently feasible in patients with sustained disease control, whereas adverse events were primarily associated with prolonged treatment exposure. This study demonstrates that Denosumab is used across several distinct clinical indications in GCTB. High recurrence rates were observed following short-course neoadjuvant treatment prior to curettage, whereas prolonged disease control was frequently achieved in selected patients receiving definitive or long-term Denosumab. A preliminary clinical framework for indication-specific Denosumab use is proposed and warrants prospective validation.
2026-07-01 | Giant Cell Tumor of the Cervical Axis Treated With Anterior-Posterior Surgery and Denosumab: A Ten-year Follow-up Case Report.
Giant cell tumor of the bone (GCTB) is a benign but locally aggressive neoplasm that rarely involves the cervical spine, accounting for approximately 1-4% of all primary bone tumors. The cervical axis (C2) is an exceptionally rare site, presenting unique surgical challenges due to its complex anatomy and proximity to vital neurovascular structures. Denosumab, a monoclonal antibody targeting RANKL, has emerged as an important adjuvant therapy for unresectable or surgically challenging GCTB. Long-term outcomes of combined surgical resection and denosumab therapy in cervical spine GCTB remain poorly documented. We report the case of a 16-year-old Japanese male with a history of malignant lymphoma who presented with neck pain and a lytic lesion of the C2 vertebral body. Imaging revealed a 3.5×2.8×2.5 cm expansile lesion with extraosseous extension and encasement of the right vertebral artery. Biopsy confirmed GCTB. The patient received preoperative denosumab (120 mg on days 1, 8, and 15 of month 1, then monthly for 7 additional months) followed by right vertebral artery embolization. A two-stage anterior-posterior surgical resection was performed via mandibular osteotomy, with C1 lateral mass and C3 pedicle screw fixation and tricortical iliac crest autograft reconstruction. Postoperative denosumab (120 mg monthly) was continued for 16 months. At 10-year follow-up, the patient remains recurrence-free with solid bony fusion, no neurological deficits, and excellent functional outcomes (VAS 0/10, JOA score 17/17). This case demonstrates that combined anterior-posterior surgical resection with perioperative denosumab therapy can achieve excellent long-term tumor control and functional outcomes in C2 GCTB. Extended preoperative denosumab facilitated tumor ossification and surgical resection, while postoperative denosumab may reduce recurrence risk. Long-term surveillance remains essential given the variable recurrence patterns in spinal GCTB.
2026-05-25 | Metachronous multicentric giant cell tumor of bone with pulmonary metastases: a case report with 20-year follow-up.
Giant cell tumor of bone (GCTB) is typically a solitary lesion, with multicentric metachronous GCTB (MGCTB) accompanied by pulmonary metastasis being exceedingly rare and posing notable management challenges. A case of MGCTB with 20 years follow up at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology is reported, and relevant literatures are reviewed. This report details a 38-year-old male with MGCTB and pulmonary metastases, followed for over 20 years since his initial treatment in 2005. Despite multiple surgical interventions, including curettage, resection, and eventual amputation, the disease progressed with new osteolytic lesions emerging years later. Systemic therapy with denosumab, initiated in 2017, achieved sustained disease stabilization. Following a treatment interruption during the COVID-19 pandemic, denosumab was resumed in 2021 and effectively controlled systemic lesions; however, a persistently progressing rib lesion necessitated wide en bloc resection in 2022. To date, the patient continues on denosumab with well-controlled disease and no evidence of progression, illustrating its critical role in achieving long-term control in this rare, aggressive GCTB variant. MGCTB is extremely rare. This case underscores the importance of continuous systemic therapy in managing MGCTB, even in the context of surgical interventions.
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2026-03-24 | Giant cell tumor of bone inhibits osteoblastogenesis via WNT5B.
Giant cell tumor of bone (GCTB) induces overproduction of bone-resorbing osteoclasts through receptor activator of nuclear factor kappa B ligand (RANKL), leading to bone resorption and destruction. Consequently, denosumab, a neutralizing antibody against RANKL (a cytokine essential for osteoclast induction), is used to treat patients with GCTB. However, the activity of bone formation in GCTB remains poorly understood. Here, we show that GCTB antagonizes bone formation by expressing WNT5B, which inhibits bone formation. Co-culture of NCC-GCTB1-C1 (GCTB1s), a human GCTB cell line, with human adipose-derived stem cells (ADSCs) was performed with osteoblast induction medium. To identify the inhibitors of osteoblast differentiation, we reanalyzed the single-cell RNA sequencing data that was previously published. In addition, we performed spatial transcriptome analysis (Visium) against the section of paraffin block of GCTB. The targeted protein was knocked out using CRISPR/Cas9 and co-culture was performed. Co-culture of GCTB1s with ADSCs significantly inhibited mineralization of ADSCs. Reanalysis of single-cell RNA sequencing data indicated that GCTB tumors express WNT5B, and we observed that GCTB1s express WNT5B. We then knocked out WNT5B in GCTB1s using CRISPR/Cas9 and co-cultured them with ADSCs and observed significant rescue of mineralization in ADSCs relative to ADSCs cultured with GCTB1s expressing WNT5B. We also show that ADSC supernatants induce mineralization of GCTB1s. These studies indicate that GCTB not only induces osteoclasts, but also possesses activity that inhibits bone formation.
2024-08-15 | H3.3-G34W in giant cell tumor of bone functionally aligns with the exon choice repressor hnRNPA1L2.
RNA processing is an essential post-transcriptional phenomenon that provides the necessary complexity of transcript diversity prior to translation. Aberrations in this process could contribute to tumourigenesis, and we have previously reported increased splicing alterations in giant cell tumor of bone (GCTB), which carries mutations in the histone variant H3.3 encoding glycine 34 substituted for tryptophan (H3.3-G34W). G34W interacts with several splicing factors, most notably the trans-acting splicing factor hnRNPA1L2. To gain a deeper understanding of RNA processing in GCTB and isogenic HeLa cells with H3.3-G34W, we generated RNA-immunoprecipitation sequencing data from hnRNPA1L2 and H3.3-G34W associated RNAs, which showed that 80% overlapped across genic regions and were frequently annotated as E2F transcription factor binding sites. Splicing aberrations in both GCTB and HeLa cells with H3.3-G34W were significantly enriched for known hnRNPA1L2 binding motifs (p value < 0.01). This splicing aberration differed from hnRNPA1L2 knockouts, which showed alterations independent of H3.3-G34W. Of functional significance, hnRNPA1L2 was redistributed to closely match the H3.3 pattern, likely driven by G34W, and to loci not occupied in normal parental cells. Taken together, our data reveal a functional overlap between hnRNPA1L2 and H3.3-G34W with likely significant consequences for RNA processing during GCTB pathogenesis. This provides novel opportunities for therapeutic intervention in future modus operandi.
2024-02-01 | Association of miRNA and Bone Tumors: Future Therapeutic Inroads.
Small endogenous non-coding RNA molecules known as micro-ribonucleic acids (miRNAs) control post-transcriptional gene regulation. A change in miRNA expression is related to various diseases, including bone tumors. Benign bone tumors are categorized based on matrix production and predominant cell type. Osteochondromas and giant cell tumors are among the most common bone tumors. Interestingly, miRNAs can function as either tumor suppressor genes or oncogenes, thereby determining the fate of a tumor. In the present review, we discuss various bone tumors with regard to their prognosis, pathogenesis, and diagnosis. The association between miRNAs and bone tumors, such as osteosarcoma, Ewing's sarcoma, chondrosarcoma, and giant-cell tumors, is also discussed. Moreover, miRNA may play an important role in tumor proliferation, growth, and metastasis. Knowledge of the dysregulation, amplification, and deletion of miRNA can be beneficial for the treatment of various bone cancers. The miRNAs could be beneficial for prognosis, treatment, future drug design, and treatment of resistant cases of bone cancer.
2021-07-09 | microRNAs and bone tumours: Role of tiny molecules in the development and progression of chondrosarcoma, of giant cell tumour of bone and of Ewing's sarcoma.
The increasing interest on microRNAs (miRNAs), small non-coding RNA molecules containing about 22 nucleotides, about their biological functions led researchers to discover that they are actively involved in several biological processes. In the last decades, miRNAs become one of the most topic of cancer research. miRNAs, thanks to their function, are the perfect molecules to modulate multiple signaling pathways and gene expression in cancer, with the consequent capacity to modulate cancerous processes, such as cellular proliferation, invasion, metastasis and chemoresistance in various tumours. In the last years, several studies have demonstrated the role of miRNAs in their pathophysiology, but little we know about the underlying mechanism that lead to bone tumours like chondrosarcoma (COS), giant cell tumour of bone (GCTB) and Ewing sarcoma (EWS) to still be highly aggressive and resistant tumours. An exploration of the role of miRNAs in the biology of them will permit to researchers to find new molecular mechanisms that can be used to develop new and more effective therapies against these bone tumours. Here we present a comprehensive study of the latest discoveries which have been performed in relation to the role of miRNAs in the neoplastic processes which characterize COS, EWS and GCTB, demonstrating how these tiny molecules can act as tumour promoters or as tumour suppressors and how they can be used for improving therapeutic approaches.
2020-03-10 | Expression profiles of miRNAs in giant cell tumor of bone showed miR‐187‐5p and miR‐1323 can regulate biological functions through inhibiting FRS2
Abstract Background Giant cell tumor of bone (GCTB) is considered to be a kind of borderline tumor, which has a tendency to recur and translocate. MicroRNAs are one type of small noncoding RNA, which can inhibit the translation of targeted mRNA through RNA‐induced silencing complex. Methods Microarray was conducted on three groups of tumor tissues and normal tissues from patients with GCTB, and results showed different expression profiles of miRNAs with Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis. The functions of miR‐187‐5p and miR‐1323, which were highly expressed in GCTB, were examined by 5‐ethynyl‐2′‐deoxyuridine (EDU), transwell, and CCK8 assays. RNAhybrid et al. ( RNA prediction softwares) predicted that the two microRNAs targeted fibroblast growth factor receptor substrate 2 (FRS2), which was verified by luciferase assay and rescue experiments. Results miR‐187‐5p and miR‐1323 were highly expressed in tumor tissues. They can jointly regulate the biological functions of GCTB in vitro. Luciferase assay confirmed that the two microRNAs can bind to the 3′ untranslated regions (UTR) of mRNA of FRS2. And, rescue experiments verified the relationships between the two microRNAs and FRS2. Conclusion There were some different‐expressed microRNAs between GCTB and normal tissues. miR‐187‐5p and miR‐1323 can regulate the biological functions of GCTB through influencing the expression of FRS2.
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Drug Discovery Landscape
1 orphan drug designation for Giant cell tumor of bone, including 1 approved therapy.
1 orphan drug designation for Giant cell tumor of bone, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
denosumab [Xgeva] | antibodies | FDA | 2010-12-20 | 2013-06-13 | Amgen, Inc. |
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