RARE DISEASE
Chondrosarcoma
Chondrosarcoma
Chondrosarcoma
Drug discovery
6
drugs
With orphan designations
Overview
Chondrosarcoma is a malignant bone tumor arising from cartilage-producing cells, representing ~10% of primary bone cancers [6][9]. It predominantly affects adults aged 40-75 (mean 51) [9][12], with 1-3 cases per 200,000 annually [5][7][9]. Conventional subtypes (85% of cases) grow slowly, while rare variants like dedifferentiated (10%) and mesenchymal chondrosarcoma show aggressive behavior [5][9]. Diagnosis requires histopathology and imaging correlation [6], with surgical resection remaining the cornerstone of treatment due to inherent chemoresistance and radioresistance [3][5][8].
Categories: rare bone diseases, rare neoplastic diseases
Research Papers
2,267 drug discovery papers related to Chondrosarcoma, with 5 first-in-class and 0 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2,267 drug discovery papers related to Chondrosarcoma, with 5 first-in-class and 0 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
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.
2026-07-02 | Identification of immunopeptides (pHLA) as candidate therapeutic targets in chondrosarcoma
Background Chondrosarcoma (CHS) is the second most common primary malignant bone tumor and remains resistant to conventional therapies, underscoring the need to discover novel therapeutic targets. Cancer/testis antigens (CTAs), a class of tumor-associated proteins, represent attractive antigens for cancer immunotherapies such as adoptive T cell therapy. However, the expression profile of CTAs and their associated targetable immunopeptides presented in the Human Leukocyte Antigen-I context (pHLA) remain unknown in CHS. This study aims to characterize the CTA expression profile according to the tumor immune phenotype and clinical outcomes, and to identify the most relevant pHLA to target in CHS. Method We analyzed the CTA expression profile in tumors from 63 conventional CHS patients and in healthy tissues using GTEx and HPA databases to identify CHS-associated CTAs. Cox proportional hazards models combined with hierarchical clustering were used to correlate CTA expression with the overall survival of patients. The tumor immune phenotype was estimated based on immune gene expression signatures using a deconvolution method and a Pearson correlation coefficient matrix. The CTA-derived pHLA were characterized using immunopeptidomic profiling based on HLA-I immunoprecipitation and mass spectrometry in grade 2 and 3 CHS models. NetMHC was used to predict the binding affinity of identified pHLA to the HLA-A*02:01 and HLA-A*01:01 alleles. Results We identified a poor prognosis CTA signature predominantly associated with a non-inflamed tumor immunophenotype. Immunopeptidomic profiling revealed broad pHLA repertoires, including previously well-characterized CTAs from PRAME, CTAG2 and the MAGE-A family, as well as newly identified candidates with strong predicted HLA-binding affinity from CTAs such as HHIPL2, DBF4, BRIP1, CBX2 and DIAPH3. Conclusion This study provides the first atlas of pHLA in CHS and suggests specific antigenic targets for TCR-T cell therapies and targeted therapies such as antibody-drug conjugates.
2026-06-27 | REGγ Suppresses Ferroptosis and Induces Drug Resistance by Degrading WDR6 in Chondrosarcoma.
Chondrosarcoma (CS) is a malignant bone tumor for which treatment efficacy remains clinically challenging owing to chemotherapy resistance. Ferroptosis, an iron-dependent form of regulated cell death initiated by lipid peroxidation, has emerged as a promising strategy for addressing drug resistance. However, the potential of targeting ferroptosis to overcome drug resistance in CS has not been systematically elucidated. Our study identifies REGγ as a critical driver of malignant progression in chondrosarcoma, with its elevated expression correlating with unfavorable patient outcomes. Loss of REGγ potentiates lipid peroxidation and modulates the activation of ferroptosis-associated genes by enhancing WDR6 protein stability. Mechanistically, REGγ degrades WDR6 through a ubiquitin-independent mechanism, inhibiting the ferroptosis pathway governed by the STK11/AMPK axis and consequently promoting tumor drug resistance. Additionally, RLY01, an inhibitor of the REGγ-20S proteasome, effectively suppresses chondrosarcoma growth and sensitizes chondrosarcoma cells to cisplatin. Collectively, REGγ emerges as a highly promising therapeutic target for improving the efficacy of cisplatin and other chemotherapies in CS.
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.
2026-07-02 | Identification of immunopeptides (pHLA) as candidate therapeutic targets in chondrosarcoma
Background Chondrosarcoma (CHS) is the second most common primary malignant bone tumor and remains resistant to conventional therapies, underscoring the need to discover novel therapeutic targets. Cancer/testis antigens (CTAs), a class of tumor-associated proteins, represent attractive antigens for cancer immunotherapies such as adoptive T cell therapy. However, the expression profile of CTAs and their associated targetable immunopeptides presented in the Human Leukocyte Antigen-I context (pHLA) remain unknown in CHS. This study aims to characterize the CTA expression profile according to the tumor immune phenotype and clinical outcomes, and to identify the most relevant pHLA to target in CHS. Method We analyzed the CTA expression profile in tumors from 63 conventional CHS patients and in healthy tissues using GTEx and HPA databases to identify CHS-associated CTAs. Cox proportional hazards models combined with hierarchical clustering were used to correlate CTA expression with the overall survival of patients. The tumor immune phenotype was estimated based on immune gene expression signatures using a deconvolution method and a Pearson correlation coefficient matrix. The CTA-derived pHLA were characterized using immunopeptidomic profiling based on HLA-I immunoprecipitation and mass spectrometry in grade 2 and 3 CHS models. NetMHC was used to predict the binding affinity of identified pHLA to the HLA-A*02:01 and HLA-A*01:01 alleles. Results We identified a poor prognosis CTA signature predominantly associated with a non-inflamed tumor immunophenotype. Immunopeptidomic profiling revealed broad pHLA repertoires, including previously well-characterized CTAs from PRAME, CTAG2 and the MAGE-A family, as well as newly identified candidates with strong predicted HLA-binding affinity from CTAs such as HHIPL2, DBF4, BRIP1, CBX2 and DIAPH3. Conclusion This study provides the first atlas of pHLA in CHS and suggests specific antigenic targets for TCR-T cell therapies and targeted therapies such as antibody-drug conjugates.
2026-06-27 | REGγ Suppresses Ferroptosis and Induces Drug Resistance by Degrading WDR6 in Chondrosarcoma.
Chondrosarcoma (CS) is a malignant bone tumor for which treatment efficacy remains clinically challenging owing to chemotherapy resistance. Ferroptosis, an iron-dependent form of regulated cell death initiated by lipid peroxidation, has emerged as a promising strategy for addressing drug resistance. However, the potential of targeting ferroptosis to overcome drug resistance in CS has not been systematically elucidated. Our study identifies REGγ as a critical driver of malignant progression in chondrosarcoma, with its elevated expression correlating with unfavorable patient outcomes. Loss of REGγ potentiates lipid peroxidation and modulates the activation of ferroptosis-associated genes by enhancing WDR6 protein stability. Mechanistically, REGγ degrades WDR6 through a ubiquitin-independent mechanism, inhibiting the ferroptosis pathway governed by the STK11/AMPK axis and consequently promoting tumor drug resistance. Additionally, RLY01, an inhibitor of the REGγ-20S proteasome, effectively suppresses chondrosarcoma growth and sensitizes chondrosarcoma cells to cisplatin. Collectively, REGγ emerges as a highly promising therapeutic target for improving the efficacy of cisplatin and other chemotherapies in CS.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
6 orphan drug designations for Chondrosarcoma.
6 orphan drug designations for Chondrosarcoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Ivosidenib | small molecules | EMA | 2024-10-11 | — | Les Laboratoires Servier |
ivosidenib | small molecules | FDA | 2023-05-17 | — | Servier Pharmaceuticals |
Humanised IgG1 tetravalent monoclonal antibody against death receptor 5 | antibodies | EMA | 2022-08-10 | — | TMC Pharma (EU) Limited |
ozekibart | antibodies | FDA | 2021-11-24 | — | Inhibrx, Inc. |
Patidegib [IPI-926] | small molecules | EMA | 2011-05-13 | — | Voisin Consulting Life Sciences |
oral potent and selective antagonist | small molecules | FDA | 2011-02-18 | — | Infinity Pharmaceuticals, Inc. |
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