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
1,894 drug discovery papers about Giant cell tumor of bone, with 4 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,894 drug discovery papers about Giant cell tumor of bone, with 4 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
cell therapies
2026-09-09 | "A Giant Shoulder": Proximal Humerus Giant Cell Tumor Managed With Extended Curettage and Proximal Humerus Internal Locking System Plating with Fibular Strut Graft - A Case Report.
Giant cell tumors of the bone (GCTB) are challenging neoplasms, particularly in the proximal humerus. We report the case of a 46-year-old male with proximal humerus GCTB who was managed with extended curettage, proximal humerus internal locking system (PHILOS) plating, and fibular strut grafting. The patient presented with shoulder pain and restricted movement. Imaging revealed a lytic lesion in the metaphyseal-epiphyseal region, and a biopsy confirmed the diagnosis. Extended curettage was performed using the deltopectoral approach, followed by cryotherapy and reconstruction with a fibular strut graft and PHILOS plate fixation. The patient received three post-operative doses of zoledronic acid. At the 24-month follow-up, the patient showed near-complete shoulder movement, with a disabilities of the arm, shoulder, and hand score of 20.8. Imaging revealed complete graft incorporation without any recurrence. This case demonstrates the effectiveness of extended curettage and biological reconstruction in managing proximal humeral GCTB, balancing tumor control and functional preservation.
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.
small molecules
2026-09-09 | Acetabular Giant Cell Tumor Presenting with Protrusio Acetabuli: A Rare Case Report.
Giant cell tumor of bone (GCTB) is a benign but locally aggressive neoplasm that predominantly affects the epiphyses of long bones. Pelvic involvement is uncommon, and acetabular GCTB presents particular diagnostic and therapeutic challenges because of the complex pelvic anatomy, proximity to neurovascular structures, and critical weight-bearing function of the hip. We report the case of a 50-year-old female who presented with progressive left hip pain, restricted movements, and inability to bear weight following a trivial fall. Radiographs and cross-sectional imaging demonstrated an extensive expansile lytic lesion involving the entire left acetabulum, with cortical thinning and breach, weight-bearing dome involvement, and protrusio acetabuli with medial migration of the femoral head. Computed tomography-guided core needle biopsy confirmed GCTB, Campanacci grade II-III. The patient underwent extended intralesional curettage using a high-speed burr with phenol as a local adjuvant. The resultant acetabular defect was reconstructed using structural corticocancellous and cancellous bone grafts, supplemented by an acetabular reinforcement cage and total hip replacement to restore acetabular stability, hip biomechanics, and limb length. At 6 months of follow-up, the patient demonstrated pain-free hip movement, restoration of limb length, satisfactory hip stability, and independent mobilization. Radiographs showed maintained implant position and no evidence of local recurrence or early mechanical failure. The functional outcome was excellent, with a Musculoskeletal Tumor Society score exceeding 25/30. Extensive acetabular GCTB with protrusio acetabuli represents a challenging surgical entity requiring individualized oncological and reconstructive planning. Extended intralesional curettage combined with local adjuvant therapy, structural bone grafting, acetabular cage reconstruction, and total hip replacement can provide satisfactory early functional and radiological outcomes in appropriately selected patients. Long-term clinical and radiographic surveillance remains essential because of the risk of delayed local recurrence and prosthetic complications.
2026-08-26 | HMGA2::NCOR2 fusion-driven giant cell tumors: Diagnosis and treatment.
Giant cell-rich tumors encompass a heterogeneous group of bone and soft tissue neoplasms with overlapping morphologic features but distinct molecular drivers and clinical behaviors. Recent studies have identified a unique subset of giant cell-rich tumors characterized by recurrent HMGA2::NCOR2 gene fusions, variably described as xanthogranulomatous epithelial tumor or keratin-positive giant cell tumor. In this paper, we emphasize the clinicopathologic, histologic, and molecular features that distinguish these rare neoplasms from conventional giant cell tumors of bone, soft tissue giant cell tumors, and tenosynovial giant cell tumors. Although these tumors generally exhibit an indolent clinical course, their optimal management remains undefined due to limited published experience. Emerging data suggest signs of therapeutic activity with targeting the CSF1 signaling pathway, and there may be a role for tyrosine kinase inhibitors such as imatinib in selected cases. In contrast, the role of denosumab in this molecularly distinct entity remains unclear. Given the rarity of HMGA2::NCOR2-rearranged tumors, improved recognition and molecular confirmation are essential to refine diagnostic criteria and guide future therapeutic strategies.
2026-08-20 | PDGFRA mediates the PI3K/AKT signaling pathway to regulate the growth and phenotype of GCTB tumor cells.
The nature of true neoplastic cells of giant cell tumor of bone (GCTB) remains unverified. As the effect of denosumab on true neoplastic cells needs to be clarified, direct targeting of these cells remains unclear. In this study, we obtained 32 formalin-fixed paraffin-embedded (FFPE) GCTB tissue blocks, performing H&E staining and immunohistochemistry staining of CD68. Multinucleated giant cells, monocytes, and CD68-negative mononuclear spindle cells were accurately captured by laser capture microdissection. The DNA of these cells was extracted, digested with HpaII and subjected to nested PCR amplification. We isolated and cultured GCTB primary tumor cells. The primary tumor cells were treated with denosumab and PDGFRA inhibitors. CCK8 assays and RT-qPCR were performed to reveal the effect of the inhibitors. In HUMARA-heterozygous samples, CD68 negative mononuclear spindle cells appeared as only one main peak after digestion, which suggests that the CD68 negative mononuclear spindle cells are monoclonal. Denosumab had no direct effect on the growth of GCTB primary tumor cells. PDGFRA inhibitor Avapritinib had a direct inhibitory effect on the growth of the tumor cells and altered the tumor cell phenotype. AKT inhibitors had a similar inhibitory effect as Avapritinib. Avapritinib altered the expression of AKT-related genes, and down-regulated pGSK3β. The downregulation of pAKT and pGSK3β was partially reversed by co-treatment with the AKT agonist SC79, suggesting PI3K/AKT as a downstream pathway of PDGFRA. CD68 negative mononuclear spindle cells are the true neoplastic cells of GCTB. PDGFRA inhibition may be a novel targeted therapy for GCTB.
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.
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
2026-09-15 | Clinicopathological characteristics of giant cell tumor of bone and identification of a novel H3F3A p.V36_K37insL mutation.
Osteoclast-rich bone lesions present overlapping clinical and radiological features, while their biological behaviors and treatment protocols differ greatly, posing challenges for differential diagnosis. H3.3G34W immunohistochemistry serves as the primary biomarker for giant cell tumor of bone (GCTB), yet this marker is not expressed in all GCTB cases. Denosumab, the first-line targeted drug, induces profound tumour remodelling that raises diagnostic difficulties for post-treatment specimens. A total of 45 osteoclast-rich bone lesions collected between 2020 and 2024 at the First Affiliated Hospital of Zhejiang University School of Medicine were retrospectively screened, with 16 cases harbouring H3F3A mutations enrolled for analysis. All hematoxylin and eosin (HE) staining and immunohistochemical (IHC) slides underwent independent review by two senior pathologists, and full imaging datasets were re-assessed by two radiologists. Sanger sequencing was performed on formalin-fixed paraffin-embedded(FFPE) specimens to identify H3F3A gene variants. Clinicopathological and radiological profiles of mutant GCTB were summarised, and histological as well as molecular changes before and after denosumab intervention were compared. Among the 45 screened lesions, 16 harboured H3F3A mutations, including 14 canonical p.G34W variants, one p.G34L variant and one previously unreported p.V36_K37insL insertion variant undetectable by routine H3.3G34W immunohistochemistry. Typical osteolytic, eccentric and expansile imaging manifestations were observed in most GCTB cases. Conventional untreated lesions exhibited characteristic evenly distributed mononuclear stromal cells and osteoclast-like giant cells. Marked depletion of giant cells, spindle cell proliferation, woven bone formation and weakened IHC staining were common histological alterations after denosumab therapy, accompanied by reduced mutant allele abundance in partial post-treatment specimens. Two patients developed local tumour recurrence during follow-up. Comprehensive integration of clinical, radiological, histological and molecular evidence is essential for accurate differential diagnosis of osteoclast-rich bone lesions after denosumab treatment. The newly identified H3F3A p.V36_K37insL variant may represent a potential rare variant for morphologically‑typical GCTB, and serve as an auxiliary molecular clue for H3.3‑G34W‑immunonegative cases. Further multicenter and functional studies are required to clarify the biological characteristics of this novel variant.
2026-09-11 | Giant Cell Tumor of the Distal Humerus: A Rare Location With a Good Response to Denosumab.
Giant cell tumors (GCTs) are rare, benign, locally aggressive neoplasms. They typically affect the metaphyseal region; their occurrence at the distal humerus is rare, making their management challenging. We report the case of a 13-year-old girl, skeletally immature, admitted for a painful, progressive mass at her right elbow (circumference 26 cm) with functional limitation. Radiological evaluation by magnetic resonance imaging (MRI revealed a large osteolytic epiphysometaphyseal lesion of the right distal humerus, centered on the medial epicondyle and measuring 36 × 35 × 60 mm, with cortical rupture and soft-tissue invasion (Campanacci grade III). The bone biopsy revealed a GCT with no signs of malignancy. The staging workup was negative. Given the complex joint location and the patient's young age, the multidisciplinary team decided to initiate anti-receptor activator of nuclear factor-κB ligand (RANKL) therapy with denosumab (70 mg/m² subcutaneously (SC)) on days 1, 8, 15, and 28, followed by monthly administration, along with calcium and vitamin D supplementation. The seven-month follow-up was favorable: regression of the swelling (circumference 20 cm), complete joint release, and lesion stability on the follow-up MRI, with no calcium-phosphate complications. Denosumab is used in situations where surgery is not an option to reduce tumor size and control its progression. Its use increases the risk of calcium-phosphorus abnormalities and growth disorders. Our case demonstrated that a well-defined treatment regimen combined with calcium-phosphorus supplementation could control the aggressiveness of GCTs.
2026-09-08 | Total en bloc resection of a giant cell tumour of the cervical spine involving the vertebral artery.
A woman in her 20s presented with neck pain and was diagnosed with a primary giant cell tumour (GCT) involving the C5 vertebral body and encasing the left vertebral artery (VA). Denosumab therapy was initiated to reduce tumour vascularity and facilitate resection. After preoperative embolisation of the left VA, total en bloc resection of the tumour was performed. Postoperatively, the patient experienced transient left upper extremity weakness, which improved significantly over time. Follow-up imaging showed successful bony fusion and no recurrence. This case highlights the importance of multidisciplinary planning in managing cervical spine GCTs involving critical neurovascular structures. Combined denosumab therapy and VA embolisation can enable safe and complete tumour resection, potentially improving outcomes and reducing recurrence risk, especially in young patients.
2026-09-06 | Multicentric metachronous giant cell tumor of the femur: a rare case report and review of the literature.
Giant cell tumor of bone (GCTB) is a benign but locally aggressive osteolytic neoplasm that most commonly presents as a solitary lesion in long bones. Multicentric GCTB is rare, comprising fewer than 1% of all cases, and metachronous involvement of two distinct regions within the same bone is exceptionally uncommon. We report the case of a 22-year-old man who initially presented with a 2-year history of right knee pain. Radiologic and histopathologic evaluation confirmed a Campanacci grade III GCTB of the distal femur, which was treated with intralesional curettage, polymethylmethacrylate augmentation, and adjuvant radiotherapy. Seven months later, he developed new-onset right hip pain. Imaging revealed a separate osteolytic lesion of the proximal femur. Histopathology confirmed a second GCTB lesion, establishing the diagnosis of multicentric metachronous disease. The development of a second histologically confirmed GCTB within the same femur shortly after treatment of the primary lesion represents a rare diagnostic and therapeutic challenge. Distinguishing metachronous multicentric disease from intramedullary skip lesions and metastatic or metabolic bone disease is critical, as management and prognosis differ substantially. The recommended treatment for GCTB is curettage, but this may not be possible when the lesion is located in the proximal femur. This case highlights an exceptionally rare presentation of a metachronous, multicentric GCTB occurring in different regions of the same long bone. Vigilant long-term radiologic surveillance is essential.
2026-08-31 | Spinopelvic Reconstruction for a Giant Cell Tumor Involving the Sacroiliac Joint: A Case Report.
Giant cell tumors of the bone (GCTB) involving the sacroiliac joint are uncommon and pose significant surgical challenges due to their proximity to major neurovascular structures and the complexity of stabilizing the pelvic. We describe a case of sacroiliac joint GCTB successfully managed with preoperative denosumab, piecemeal tumor resection, and spinopelvic reconstruction. A 34-year-old woman presented with progressive gluteal pain and swelling. Imaging demonstrated an osteolytic lesion extending from the left sacrum to the ilium with extraosseous soft-tissue involvement. Histopathology confirmed the GCTB diagnosis. To facilitate resection and reduce intraoperative blood loss, denosumab (120 mg monthly) was administered for five months, resulting in marked peripheral ossification on computed tomography. The tumor was resected via a posterior approach with preservation of the S1-S3 nerve roots. Spinopelvic reconstruction was achieved using L4-S2 fixation, S2 alar-iliac screws, artificial bone graft, and unsintered hydroxyapatite/poly-L-lactide mesh. The postoperative course was uneventful, and no neurological deficits were observed. Follow-up computed tomography at three months and one year demonstrated stable instrumentation, preserved graft integrity, and no evidence of local recurrence. Preoperative denosumab followed by posterior tumor resection and spinopelvic reconstruction provided excellent short-term tumor control and functional recovery in this patient with sacroiliac joint GCTB. Given the high recurrence risk associated with pelvic lesions, continued long-term surveillance is essential.
other
2026-05-14 | Combined Post-operative Denosumab and Oral Bisphosphonate Therapy Following Resection of Spinal Giant Cell Tumor: A Case Report.
Giant cell tumor (GCT) of the spine is a rare, locally aggressive bone tumor with a high risk of recurrence, particularly when wide surgical margins cannot be achieved. Although en bloc spondylectomy provides the best oncological control, it is frequently not feasible due to anatomical constraints. Systemic adjuvants have therefore been explored to reduce recurrence risk. Denosumab suppresses osteoclast-mediated bone resorption, while bisphosphonates exert direct anti-tumor effects on neoplastic stromal cells. However, the intentional combined post-operative use of denosumab and oral bisphosphonate therapy in spinal GCT (SGCT) has not been previously reported. This case highlights the feasibility and biological rationale of this combined adjuvant strategy. A 27-year-old male presented with severe low back pain and bilateral lower limb radicular pain of 6 months' duration. Imaging demonstrated a destructive lesion involving the third lumbar vertebral body with paravertebral soft-tissue extension. A diagnosis of Enneking stage III GCT was made after biopsy. The patient received pre-operative denosumab followed by gross total resection of the affected vertebra with posterior stabilization and anterior column reconstruction. Postoperatively, denosumab therapy was continued for 6 months, and the patient was simultaneously commenced on oral bisphosphonate therapy (weekly alendronate followed by monthly ibandronate). The patient had complete resolution of symptoms. Serial imaging demonstrated progressive osseous consolidation and stable instrumentation with no evidence of residual or recurrent disease. At 4½ years of follow-up, the patient remained radiologically disease free without treatment-related adverse events. This report demonstrates the feasibility of combining post-operative denosumab and oral bisphosphonate therapy as an adjuvant strategy for high-risk SGCT when wide surgical margins are not achievable. By targeting different cellular pathways involved in tumor biology, this approach may provide complementary tumor control, thereby reducing the risk of recurrence.
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.
cell therapies
2026-09-09 | "A Giant Shoulder": Proximal Humerus Giant Cell Tumor Managed With Extended Curettage and Proximal Humerus Internal Locking System Plating with Fibular Strut Graft - A Case Report.
Giant cell tumors of the bone (GCTB) are challenging neoplasms, particularly in the proximal humerus. We report the case of a 46-year-old male with proximal humerus GCTB who was managed with extended curettage, proximal humerus internal locking system (PHILOS) plating, and fibular strut grafting. The patient presented with shoulder pain and restricted movement. Imaging revealed a lytic lesion in the metaphyseal-epiphyseal region, and a biopsy confirmed the diagnosis. Extended curettage was performed using the deltopectoral approach, followed by cryotherapy and reconstruction with a fibular strut graft and PHILOS plate fixation. The patient received three post-operative doses of zoledronic acid. At the 24-month follow-up, the patient showed near-complete shoulder movement, with a disabilities of the arm, shoulder, and hand score of 20.8. Imaging revealed complete graft incorporation without any recurrence. This case demonstrates the effectiveness of extended curettage and biological reconstruction in managing proximal humeral GCTB, balancing tumor control and functional preservation.
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.
small molecules
2026-09-09 | Acetabular Giant Cell Tumor Presenting with Protrusio Acetabuli: A Rare Case Report.
Giant cell tumor of bone (GCTB) is a benign but locally aggressive neoplasm that predominantly affects the epiphyses of long bones. Pelvic involvement is uncommon, and acetabular GCTB presents particular diagnostic and therapeutic challenges because of the complex pelvic anatomy, proximity to neurovascular structures, and critical weight-bearing function of the hip. We report the case of a 50-year-old female who presented with progressive left hip pain, restricted movements, and inability to bear weight following a trivial fall. Radiographs and cross-sectional imaging demonstrated an extensive expansile lytic lesion involving the entire left acetabulum, with cortical thinning and breach, weight-bearing dome involvement, and protrusio acetabuli with medial migration of the femoral head. Computed tomography-guided core needle biopsy confirmed GCTB, Campanacci grade II-III. The patient underwent extended intralesional curettage using a high-speed burr with phenol as a local adjuvant. The resultant acetabular defect was reconstructed using structural corticocancellous and cancellous bone grafts, supplemented by an acetabular reinforcement cage and total hip replacement to restore acetabular stability, hip biomechanics, and limb length. At 6 months of follow-up, the patient demonstrated pain-free hip movement, restoration of limb length, satisfactory hip stability, and independent mobilization. Radiographs showed maintained implant position and no evidence of local recurrence or early mechanical failure. The functional outcome was excellent, with a Musculoskeletal Tumor Society score exceeding 25/30. Extensive acetabular GCTB with protrusio acetabuli represents a challenging surgical entity requiring individualized oncological and reconstructive planning. Extended intralesional curettage combined with local adjuvant therapy, structural bone grafting, acetabular cage reconstruction, and total hip replacement can provide satisfactory early functional and radiological outcomes in appropriately selected patients. Long-term clinical and radiographic surveillance remains essential because of the risk of delayed local recurrence and prosthetic complications.
2026-08-26 | HMGA2::NCOR2 fusion-driven giant cell tumors: Diagnosis and treatment.
Giant cell-rich tumors encompass a heterogeneous group of bone and soft tissue neoplasms with overlapping morphologic features but distinct molecular drivers and clinical behaviors. Recent studies have identified a unique subset of giant cell-rich tumors characterized by recurrent HMGA2::NCOR2 gene fusions, variably described as xanthogranulomatous epithelial tumor or keratin-positive giant cell tumor. In this paper, we emphasize the clinicopathologic, histologic, and molecular features that distinguish these rare neoplasms from conventional giant cell tumors of bone, soft tissue giant cell tumors, and tenosynovial giant cell tumors. Although these tumors generally exhibit an indolent clinical course, their optimal management remains undefined due to limited published experience. Emerging data suggest signs of therapeutic activity with targeting the CSF1 signaling pathway, and there may be a role for tyrosine kinase inhibitors such as imatinib in selected cases. In contrast, the role of denosumab in this molecularly distinct entity remains unclear. Given the rarity of HMGA2::NCOR2-rearranged tumors, improved recognition and molecular confirmation are essential to refine diagnostic criteria and guide future therapeutic strategies.
2026-08-20 | PDGFRA mediates the PI3K/AKT signaling pathway to regulate the growth and phenotype of GCTB tumor cells.
The nature of true neoplastic cells of giant cell tumor of bone (GCTB) remains unverified. As the effect of denosumab on true neoplastic cells needs to be clarified, direct targeting of these cells remains unclear. In this study, we obtained 32 formalin-fixed paraffin-embedded (FFPE) GCTB tissue blocks, performing H&E staining and immunohistochemistry staining of CD68. Multinucleated giant cells, monocytes, and CD68-negative mononuclear spindle cells were accurately captured by laser capture microdissection. The DNA of these cells was extracted, digested with HpaII and subjected to nested PCR amplification. We isolated and cultured GCTB primary tumor cells. The primary tumor cells were treated with denosumab and PDGFRA inhibitors. CCK8 assays and RT-qPCR were performed to reveal the effect of the inhibitors. In HUMARA-heterozygous samples, CD68 negative mononuclear spindle cells appeared as only one main peak after digestion, which suggests that the CD68 negative mononuclear spindle cells are monoclonal. Denosumab had no direct effect on the growth of GCTB primary tumor cells. PDGFRA inhibitor Avapritinib had a direct inhibitory effect on the growth of the tumor cells and altered the tumor cell phenotype. AKT inhibitors had a similar inhibitory effect as Avapritinib. Avapritinib altered the expression of AKT-related genes, and down-regulated pGSK3β. The downregulation of pAKT and pGSK3β was partially reversed by co-treatment with the AKT agonist SC79, suggesting PI3K/AKT as a downstream pathway of PDGFRA. CD68 negative mononuclear spindle cells are the true neoplastic cells of GCTB. PDGFRA inhibition may be a novel targeted therapy for GCTB.
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.
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
2026-09-15 | Clinicopathological characteristics of giant cell tumor of bone and identification of a novel H3F3A p.V36_K37insL mutation.
Osteoclast-rich bone lesions present overlapping clinical and radiological features, while their biological behaviors and treatment protocols differ greatly, posing challenges for differential diagnosis. H3.3G34W immunohistochemistry serves as the primary biomarker for giant cell tumor of bone (GCTB), yet this marker is not expressed in all GCTB cases. Denosumab, the first-line targeted drug, induces profound tumour remodelling that raises diagnostic difficulties for post-treatment specimens. A total of 45 osteoclast-rich bone lesions collected between 2020 and 2024 at the First Affiliated Hospital of Zhejiang University School of Medicine were retrospectively screened, with 16 cases harbouring H3F3A mutations enrolled for analysis. All hematoxylin and eosin (HE) staining and immunohistochemical (IHC) slides underwent independent review by two senior pathologists, and full imaging datasets were re-assessed by two radiologists. Sanger sequencing was performed on formalin-fixed paraffin-embedded(FFPE) specimens to identify H3F3A gene variants. Clinicopathological and radiological profiles of mutant GCTB were summarised, and histological as well as molecular changes before and after denosumab intervention were compared. Among the 45 screened lesions, 16 harboured H3F3A mutations, including 14 canonical p.G34W variants, one p.G34L variant and one previously unreported p.V36_K37insL insertion variant undetectable by routine H3.3G34W immunohistochemistry. Typical osteolytic, eccentric and expansile imaging manifestations were observed in most GCTB cases. Conventional untreated lesions exhibited characteristic evenly distributed mononuclear stromal cells and osteoclast-like giant cells. Marked depletion of giant cells, spindle cell proliferation, woven bone formation and weakened IHC staining were common histological alterations after denosumab therapy, accompanied by reduced mutant allele abundance in partial post-treatment specimens. Two patients developed local tumour recurrence during follow-up. Comprehensive integration of clinical, radiological, histological and molecular evidence is essential for accurate differential diagnosis of osteoclast-rich bone lesions after denosumab treatment. The newly identified H3F3A p.V36_K37insL variant may represent a potential rare variant for morphologically‑typical GCTB, and serve as an auxiliary molecular clue for H3.3‑G34W‑immunonegative cases. Further multicenter and functional studies are required to clarify the biological characteristics of this novel variant.
2026-09-11 | Giant Cell Tumor of the Distal Humerus: A Rare Location With a Good Response to Denosumab.
Giant cell tumors (GCTs) are rare, benign, locally aggressive neoplasms. They typically affect the metaphyseal region; their occurrence at the distal humerus is rare, making their management challenging. We report the case of a 13-year-old girl, skeletally immature, admitted for a painful, progressive mass at her right elbow (circumference 26 cm) with functional limitation. Radiological evaluation by magnetic resonance imaging (MRI revealed a large osteolytic epiphysometaphyseal lesion of the right distal humerus, centered on the medial epicondyle and measuring 36 × 35 × 60 mm, with cortical rupture and soft-tissue invasion (Campanacci grade III). The bone biopsy revealed a GCT with no signs of malignancy. The staging workup was negative. Given the complex joint location and the patient's young age, the multidisciplinary team decided to initiate anti-receptor activator of nuclear factor-κB ligand (RANKL) therapy with denosumab (70 mg/m² subcutaneously (SC)) on days 1, 8, 15, and 28, followed by monthly administration, along with calcium and vitamin D supplementation. The seven-month follow-up was favorable: regression of the swelling (circumference 20 cm), complete joint release, and lesion stability on the follow-up MRI, with no calcium-phosphate complications. Denosumab is used in situations where surgery is not an option to reduce tumor size and control its progression. Its use increases the risk of calcium-phosphorus abnormalities and growth disorders. Our case demonstrated that a well-defined treatment regimen combined with calcium-phosphorus supplementation could control the aggressiveness of GCTs.
2026-09-08 | Total en bloc resection of a giant cell tumour of the cervical spine involving the vertebral artery.
A woman in her 20s presented with neck pain and was diagnosed with a primary giant cell tumour (GCT) involving the C5 vertebral body and encasing the left vertebral artery (VA). Denosumab therapy was initiated to reduce tumour vascularity and facilitate resection. After preoperative embolisation of the left VA, total en bloc resection of the tumour was performed. Postoperatively, the patient experienced transient left upper extremity weakness, which improved significantly over time. Follow-up imaging showed successful bony fusion and no recurrence. This case highlights the importance of multidisciplinary planning in managing cervical spine GCTs involving critical neurovascular structures. Combined denosumab therapy and VA embolisation can enable safe and complete tumour resection, potentially improving outcomes and reducing recurrence risk, especially in young patients.
2026-09-06 | Multicentric metachronous giant cell tumor of the femur: a rare case report and review of the literature.
Giant cell tumor of bone (GCTB) is a benign but locally aggressive osteolytic neoplasm that most commonly presents as a solitary lesion in long bones. Multicentric GCTB is rare, comprising fewer than 1% of all cases, and metachronous involvement of two distinct regions within the same bone is exceptionally uncommon. We report the case of a 22-year-old man who initially presented with a 2-year history of right knee pain. Radiologic and histopathologic evaluation confirmed a Campanacci grade III GCTB of the distal femur, which was treated with intralesional curettage, polymethylmethacrylate augmentation, and adjuvant radiotherapy. Seven months later, he developed new-onset right hip pain. Imaging revealed a separate osteolytic lesion of the proximal femur. Histopathology confirmed a second GCTB lesion, establishing the diagnosis of multicentric metachronous disease. The development of a second histologically confirmed GCTB within the same femur shortly after treatment of the primary lesion represents a rare diagnostic and therapeutic challenge. Distinguishing metachronous multicentric disease from intramedullary skip lesions and metastatic or metabolic bone disease is critical, as management and prognosis differ substantially. The recommended treatment for GCTB is curettage, but this may not be possible when the lesion is located in the proximal femur. This case highlights an exceptionally rare presentation of a metachronous, multicentric GCTB occurring in different regions of the same long bone. Vigilant long-term radiologic surveillance is essential.
2026-08-31 | Spinopelvic Reconstruction for a Giant Cell Tumor Involving the Sacroiliac Joint: A Case Report.
Giant cell tumors of the bone (GCTB) involving the sacroiliac joint are uncommon and pose significant surgical challenges due to their proximity to major neurovascular structures and the complexity of stabilizing the pelvic. We describe a case of sacroiliac joint GCTB successfully managed with preoperative denosumab, piecemeal tumor resection, and spinopelvic reconstruction. A 34-year-old woman presented with progressive gluteal pain and swelling. Imaging demonstrated an osteolytic lesion extending from the left sacrum to the ilium with extraosseous soft-tissue involvement. Histopathology confirmed the GCTB diagnosis. To facilitate resection and reduce intraoperative blood loss, denosumab (120 mg monthly) was administered for five months, resulting in marked peripheral ossification on computed tomography. The tumor was resected via a posterior approach with preservation of the S1-S3 nerve roots. Spinopelvic reconstruction was achieved using L4-S2 fixation, S2 alar-iliac screws, artificial bone graft, and unsintered hydroxyapatite/poly-L-lactide mesh. The postoperative course was uneventful, and no neurological deficits were observed. Follow-up computed tomography at three months and one year demonstrated stable instrumentation, preserved graft integrity, and no evidence of local recurrence. Preoperative denosumab followed by posterior tumor resection and spinopelvic reconstruction provided excellent short-term tumor control and functional recovery in this patient with sacroiliac joint GCTB. Given the high recurrence risk associated with pelvic lesions, continued long-term surveillance is essential.
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2026-05-14 | Combined Post-operative Denosumab and Oral Bisphosphonate Therapy Following Resection of Spinal Giant Cell Tumor: A Case Report.
Giant cell tumor (GCT) of the spine is a rare, locally aggressive bone tumor with a high risk of recurrence, particularly when wide surgical margins cannot be achieved. Although en bloc spondylectomy provides the best oncological control, it is frequently not feasible due to anatomical constraints. Systemic adjuvants have therefore been explored to reduce recurrence risk. Denosumab suppresses osteoclast-mediated bone resorption, while bisphosphonates exert direct anti-tumor effects on neoplastic stromal cells. However, the intentional combined post-operative use of denosumab and oral bisphosphonate therapy in spinal GCT (SGCT) has not been previously reported. This case highlights the feasibility and biological rationale of this combined adjuvant strategy. A 27-year-old male presented with severe low back pain and bilateral lower limb radicular pain of 6 months' duration. Imaging demonstrated a destructive lesion involving the third lumbar vertebral body with paravertebral soft-tissue extension. A diagnosis of Enneking stage III GCT was made after biopsy. The patient received pre-operative denosumab followed by gross total resection of the affected vertebra with posterior stabilization and anterior column reconstruction. Postoperatively, denosumab therapy was continued for 6 months, and the patient was simultaneously commenced on oral bisphosphonate therapy (weekly alendronate followed by monthly ibandronate). The patient had complete resolution of symptoms. Serial imaging demonstrated progressive osseous consolidation and stable instrumentation with no evidence of residual or recurrent disease. At 4½ years of follow-up, the patient remained radiologically disease free without treatment-related adverse events. This report demonstrates the feasibility of combining post-operative denosumab and oral bisphosphonate therapy as an adjuvant strategy for high-risk SGCT when wide surgical margins are not achievable. By targeting different cellular pathways involved in tumor biology, this approach may provide complementary tumor control, thereby reducing the risk of recurrence.
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.
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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 | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
denosumab [Xgeva] | antibodies | FDA | Approved | Amgen, Inc. |
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