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
2,284 drug discovery papers about Chondrosarcoma, with 5 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,284 drug discovery papers about Chondrosarcoma, with 5 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-14 | Vitamin D decreases tumor cell growth and invasiveness in primary malignant bone tumors in vitro.
Primary malignant bone tumors (PMBTs) are rare neoplasms arising from bone tissue. Limited evidence suggests an association between reduced serum 25(OH) vitamin D3 levels and PMBT incidence. The active metabolite 1,25(OH)2 vitamin D3 (1,25D3) modulates tumor cell proliferation, apoptosis, and migration through interactions with the vitamin D receptor (VDR). This study investigated the effects of 1,25D3 on osteosarcoma (MG-63, SaOS-2), chondrosarcoma (SW-1353), and Ewing's sarcoma (RD-ES) cell lines. Expression of key components of vitamin D metabolism, including 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), VDR, protein disulfide-isomerase A3 (PDIA3), and the 1,25D3-responsive bone gamma-carboxyglutamate protein (BGLAP), was analyzed at mRNA and protein levels. VDR nuclear translocation was assessed by Western blotting. Cell viability, cell cycle progression, apoptosis, and migration were evaluated using metabolic assays, flow cytometry, immunocytochemistry, wound healing, and live-cell imaging. Treatment with 1,25D3 upregulated CYP24A1 in osteosarcoma cells, while BGLAP expression was detected in both osteosarcoma and SW-1353 cells. All examined cell lines expressed VDR and PDIA3, and 1,25D3 induced VDR nuclear translocation. MG-63 cell viability decreased by 23%, whereas SW-1353 cell viability decreased by 10%, with no significant changes observed in SaOS-2 and RD-ES cells. In MG-63 cells, 1,25D3 induced a significant accumulation of cells in the G1 phase, consistent with cell-cycle arrest, whereas only minor cell-cycle alterations were observed in the other cell lines. Interestingly, 1,25D3 reduced the proportion of apoptotic osteosarcoma cells by 18-30%. The migration of MG-63 cells was significantly reduced by 1,25D3, and an inhibitory trend, albeit not statistically significant, was also observed in RD-ES cells. In conclusion, 1,25D3 modulated cell viability, apoptosis, and migration in PMBT cell models, with distinct, cell-type-specific responses. These findings suggest a potential role for 1,25D3 in regulating PMBT growth and invasiveness.
2026-08-06 | Chondrosarcoma: A comprehensive review of tumor biology, clinical behavior, and therapeutic advances.
Chondrosarcoma is a heterogeneous group of malignant bone tumors characterized by the production of neoplastic hyaline cartilage. These tumors are often indolent and typically resistant to conventional chemotherapy and radiotherapy, with surgical resection remaining the cornerstone of treatment. However, patients with unresectable or metastatic disease face poor outcomes due to the lack of effective systemic therapies. While advancements in systemic treatments - such as immunotherapy and anti-angiogenic agents - and novel radiation modalities like proton beam therapy and carbon ion therapy have shown some benefit in select cases, their overall efficacy remains limited, underscoring the urgent need for more effective treatment options. Emerging novel therapies are beginning to illuminate potential new treatment pathways. Current efforts are increasingly focused on targeting recurrent genetic alterations and dysregulated signaling pathways, including IDH mutations, DR5-mediated apoptotic pathway, hedgehog signaling, Src kinase pathway, the PI3K-Akt-mTOR axis, histone deacetylation, and angiogenesis. Although these targeted strategies are still under investigation, they show promise in overcoming therapeutic resistance and advancing personalized treatment. This review provides an overview of the clinical characteristics of major chondrosarcoma subtypes, key genetic alterations implicated in tumor pathogenesis, and recent advances in treatment strategies, including surgery, chemotherapy, radiotherapy, immunotherapy, and emerging targeted therapies.
2026-07-29 | Dedifferentiated Chondrosarcoma: Current Advances and Future Perspectives.
Dedifferentiated chondrosarcoma (DDCS) remains one of the most aggressive and therapeutically challenging primary bone malignancies. While surgery continues to represent the cornerstone of treatment for localized disease, outcomes remain poor due to high rates of local recurrence and metastatic progression. The role of adjuvant therapies remains less clear. Radiotherapy may be considered in selected patients with unresectable tumors, positive margins, or for symptom palliation, whereas conventional chemotherapy has demonstrated inconsistent and generally limited benefit despite the use of osteosarcoma-based regimens. Recent advances in molecular profiling have improved our understanding of DDCS biology and revealed potential therapeutic opportunities. Recurrent IDH1/2 mutations appear to contribute to tumor progression and dedifferentiation and may represent actionable therapeutic targets. In our practice, comprehensive molecular profiling should be considered whenever feasible, particularly in advanced disease. Emerging evidence suggests that immunotherapy can induce durable responses in a small subset of patients, while early studies combining immune checkpoint inhibitors with antiangiogenic tyrosine kinase inhibitors have demonstrated encouraging response rates that exceed those historically achieved with chemotherapy alone. Although these findings require prospective validation, they support a shift toward biomarker-driven and combination treatment strategies.
2026-07-28 | Pharmacologic Activation of TRPA1 Induces Multi-Target Anticancer Responses via Apoptotic and Mitochondrial Pathways.
Objectives: Transient Receptor Potential Ankyrin 1 (TRPA1) has emerged as a stress-responsive ion channel involved in calcium homeostasis, redox signaling, migration, and cancer cell survival; however, the therapeutic relevance of TRPA1 activation versus inhibition remains poorly understood. In this study, we comparatively investigated the anticancer potential of the TRPA1 agonist ASP7663 and the TRPA1 antagonist HC030031 across a broad panel of human cancer cell lines. Methods: Antiproliferative and cytotoxic effects were evaluated using MTT and LDH assays, while apoptotic signaling, DNA fragmentation, mitochondrial membrane potential, migration inhibition, DNA/BSA interactions, topoisomerase I inhibition, and molecular docking analyses were comprehensively assessed. Results: ASP7663 exhibited markedly lower GI50 values than HC030031 in most cancer models and demonstrated favorable tumor selectivity relative to normal cells. Mechanistically, ASP7663 induced robust apoptotic activation characterized by significant upregulation of Caspase-3, Caspase-8, and Caspase-9, together with enhanced DNA fragmentation and pronounced nuclear condensation. Rhodamine-123 staining further revealed substantial mitochondrial membrane depolarization, indicating activation of intrinsic apoptotic pathways. In addition, ASP7663 produced selective membrane damage in malignant cells, stronger inhibition of migration in osteosarcoma and chondrosarcoma models, enhanced CT-DNA/BSA binding affinity, partial topoisomerase I inhibition, and superior docking interactions with apoptosis-related targets, including Caspase-3, Caspase-8, Caspase-9, Bax, and Bcl-2. Conclusions: Collectively, these findings suggest that ASP7663 is a promising multi-target candidate for anticancer therapy and support further investigation of TRPA1-associated pathways as potential therapeutic targets in cancer.
2026-07-28 | Targeting the Hippo/YAP-TAZ pathway increases X-ray sensitivity in chondrosarcoma spheroids and is associated with autophagic disruption.
Chondrosarcomas are malignant cartilage-forming bone tumors with limited therapeutic options, as surgical resection remains the only curative treatment, while chemo- and radiotherapy show limited efficacy due to intrinsic resistance mechanisms. Dysregulation of the Hippo signaling pathway been associated with tumor progression and therapy resistance and has emerged as a promising experimental target across several cancer entities. However, its relevance in chondrosarcoma remains unclear, particularly with regard to potential radiosensitizing effects. Human chondrosarcoma (SW-1353 and Cal78) and healthy chondrocyte (HC) spheroids were treated with Verteporfin (VP) alone or in combination with X-ray irradiation. Cell viability, Hippo/YAP-TAZ signaling, autophagy-associated markers, DNA damage, apoptosis, ultrastructural alterations, and gene expression were analyzed using ATP assays, immunoblotting, RT-qPCR, immunohistochemistry, and transmission electron microscopy. VP treatment caused a dose-dependent decline in cell proliferation and suppressed key YAP/TAZ target genes, both in chondrosarcoma cells and HC, alongside downregulation of Hippo pathway components and proliferative markers like cMyc and PCNA. Combined with X-ray irradiation, these effects were amplified, supporting a potential radiosensitizing activity of VP in this preclinical model. Ultrastructural and molecular data showed that VP disrupted autophagic balance in all cell types, leading to mitochondrial damage, lipid accumulation, and nuclear fragmentation. Despite the higher basal autophagy in HC cells, VP led to cell death involving autophagy, apoptosis, and DNA damage, evidenced by increased LC3B-II, Beclin, γH2AX, and PARP cleavage. Enhanced DNA damage markers and altered p53-MDM2 signaling after treatment reflect the genotoxic stress induced. Our data suggest that VP, particularly in combination with irradiation, is associated with disruption of multiple survival pathways in chondrosarcoma cells, offering a promising avenue for therapeutic intervention. Future studies should investigate the interplay between autophagy, apoptosis, and Hippo signaling to enable their therapeutic targeting in cancer.
2026-08-14 | Vitamin D decreases tumor cell growth and invasiveness in primary malignant bone tumors in vitro.
Primary malignant bone tumors (PMBTs) are rare neoplasms arising from bone tissue. Limited evidence suggests an association between reduced serum 25(OH) vitamin D3 levels and PMBT incidence. The active metabolite 1,25(OH)2 vitamin D3 (1,25D3) modulates tumor cell proliferation, apoptosis, and migration through interactions with the vitamin D receptor (VDR). This study investigated the effects of 1,25D3 on osteosarcoma (MG-63, SaOS-2), chondrosarcoma (SW-1353), and Ewing's sarcoma (RD-ES) cell lines. Expression of key components of vitamin D metabolism, including 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), VDR, protein disulfide-isomerase A3 (PDIA3), and the 1,25D3-responsive bone gamma-carboxyglutamate protein (BGLAP), was analyzed at mRNA and protein levels. VDR nuclear translocation was assessed by Western blotting. Cell viability, cell cycle progression, apoptosis, and migration were evaluated using metabolic assays, flow cytometry, immunocytochemistry, wound healing, and live-cell imaging. Treatment with 1,25D3 upregulated CYP24A1 in osteosarcoma cells, while BGLAP expression was detected in both osteosarcoma and SW-1353 cells. All examined cell lines expressed VDR and PDIA3, and 1,25D3 induced VDR nuclear translocation. MG-63 cell viability decreased by 23%, whereas SW-1353 cell viability decreased by 10%, with no significant changes observed in SaOS-2 and RD-ES cells. In MG-63 cells, 1,25D3 induced a significant accumulation of cells in the G1 phase, consistent with cell-cycle arrest, whereas only minor cell-cycle alterations were observed in the other cell lines. Interestingly, 1,25D3 reduced the proportion of apoptotic osteosarcoma cells by 18-30%. The migration of MG-63 cells was significantly reduced by 1,25D3, and an inhibitory trend, albeit not statistically significant, was also observed in RD-ES cells. In conclusion, 1,25D3 modulated cell viability, apoptosis, and migration in PMBT cell models, with distinct, cell-type-specific responses. These findings suggest a potential role for 1,25D3 in regulating PMBT growth and invasiveness.
2026-08-06 | Chondrosarcoma: A comprehensive review of tumor biology, clinical behavior, and therapeutic advances.
Chondrosarcoma is a heterogeneous group of malignant bone tumors characterized by the production of neoplastic hyaline cartilage. These tumors are often indolent and typically resistant to conventional chemotherapy and radiotherapy, with surgical resection remaining the cornerstone of treatment. However, patients with unresectable or metastatic disease face poor outcomes due to the lack of effective systemic therapies. While advancements in systemic treatments - such as immunotherapy and anti-angiogenic agents - and novel radiation modalities like proton beam therapy and carbon ion therapy have shown some benefit in select cases, their overall efficacy remains limited, underscoring the urgent need for more effective treatment options. Emerging novel therapies are beginning to illuminate potential new treatment pathways. Current efforts are increasingly focused on targeting recurrent genetic alterations and dysregulated signaling pathways, including IDH mutations, DR5-mediated apoptotic pathway, hedgehog signaling, Src kinase pathway, the PI3K-Akt-mTOR axis, histone deacetylation, and angiogenesis. Although these targeted strategies are still under investigation, they show promise in overcoming therapeutic resistance and advancing personalized treatment. This review provides an overview of the clinical characteristics of major chondrosarcoma subtypes, key genetic alterations implicated in tumor pathogenesis, and recent advances in treatment strategies, including surgery, chemotherapy, radiotherapy, immunotherapy, and emerging targeted therapies.
2026-07-29 | Dedifferentiated Chondrosarcoma: Current Advances and Future Perspectives.
Dedifferentiated chondrosarcoma (DDCS) remains one of the most aggressive and therapeutically challenging primary bone malignancies. While surgery continues to represent the cornerstone of treatment for localized disease, outcomes remain poor due to high rates of local recurrence and metastatic progression. The role of adjuvant therapies remains less clear. Radiotherapy may be considered in selected patients with unresectable tumors, positive margins, or for symptom palliation, whereas conventional chemotherapy has demonstrated inconsistent and generally limited benefit despite the use of osteosarcoma-based regimens. Recent advances in molecular profiling have improved our understanding of DDCS biology and revealed potential therapeutic opportunities. Recurrent IDH1/2 mutations appear to contribute to tumor progression and dedifferentiation and may represent actionable therapeutic targets. In our practice, comprehensive molecular profiling should be considered whenever feasible, particularly in advanced disease. Emerging evidence suggests that immunotherapy can induce durable responses in a small subset of patients, while early studies combining immune checkpoint inhibitors with antiangiogenic tyrosine kinase inhibitors have demonstrated encouraging response rates that exceed those historically achieved with chemotherapy alone. Although these findings require prospective validation, they support a shift toward biomarker-driven and combination treatment strategies.
2026-07-28 | Pharmacologic Activation of TRPA1 Induces Multi-Target Anticancer Responses via Apoptotic and Mitochondrial Pathways.
Objectives: Transient Receptor Potential Ankyrin 1 (TRPA1) has emerged as a stress-responsive ion channel involved in calcium homeostasis, redox signaling, migration, and cancer cell survival; however, the therapeutic relevance of TRPA1 activation versus inhibition remains poorly understood. In this study, we comparatively investigated the anticancer potential of the TRPA1 agonist ASP7663 and the TRPA1 antagonist HC030031 across a broad panel of human cancer cell lines. Methods: Antiproliferative and cytotoxic effects were evaluated using MTT and LDH assays, while apoptotic signaling, DNA fragmentation, mitochondrial membrane potential, migration inhibition, DNA/BSA interactions, topoisomerase I inhibition, and molecular docking analyses were comprehensively assessed. Results: ASP7663 exhibited markedly lower GI50 values than HC030031 in most cancer models and demonstrated favorable tumor selectivity relative to normal cells. Mechanistically, ASP7663 induced robust apoptotic activation characterized by significant upregulation of Caspase-3, Caspase-8, and Caspase-9, together with enhanced DNA fragmentation and pronounced nuclear condensation. Rhodamine-123 staining further revealed substantial mitochondrial membrane depolarization, indicating activation of intrinsic apoptotic pathways. In addition, ASP7663 produced selective membrane damage in malignant cells, stronger inhibition of migration in osteosarcoma and chondrosarcoma models, enhanced CT-DNA/BSA binding affinity, partial topoisomerase I inhibition, and superior docking interactions with apoptosis-related targets, including Caspase-3, Caspase-8, Caspase-9, Bax, and Bcl-2. Conclusions: Collectively, these findings suggest that ASP7663 is a promising multi-target candidate for anticancer therapy and support further investigation of TRPA1-associated pathways as potential therapeutic targets in cancer.
2026-07-28 | Targeting the Hippo/YAP-TAZ pathway increases X-ray sensitivity in chondrosarcoma spheroids and is associated with autophagic disruption.
Chondrosarcomas are malignant cartilage-forming bone tumors with limited therapeutic options, as surgical resection remains the only curative treatment, while chemo- and radiotherapy show limited efficacy due to intrinsic resistance mechanisms. Dysregulation of the Hippo signaling pathway been associated with tumor progression and therapy resistance and has emerged as a promising experimental target across several cancer entities. However, its relevance in chondrosarcoma remains unclear, particularly with regard to potential radiosensitizing effects. Human chondrosarcoma (SW-1353 and Cal78) and healthy chondrocyte (HC) spheroids were treated with Verteporfin (VP) alone or in combination with X-ray irradiation. Cell viability, Hippo/YAP-TAZ signaling, autophagy-associated markers, DNA damage, apoptosis, ultrastructural alterations, and gene expression were analyzed using ATP assays, immunoblotting, RT-qPCR, immunohistochemistry, and transmission electron microscopy. VP treatment caused a dose-dependent decline in cell proliferation and suppressed key YAP/TAZ target genes, both in chondrosarcoma cells and HC, alongside downregulation of Hippo pathway components and proliferative markers like cMyc and PCNA. Combined with X-ray irradiation, these effects were amplified, supporting a potential radiosensitizing activity of VP in this preclinical model. Ultrastructural and molecular data showed that VP disrupted autophagic balance in all cell types, leading to mitochondrial damage, lipid accumulation, and nuclear fragmentation. Despite the higher basal autophagy in HC cells, VP led to cell death involving autophagy, apoptosis, and DNA damage, evidenced by increased LC3B-II, Beclin, γH2AX, and PARP cleavage. Enhanced DNA damage markers and altered p53-MDM2 signaling after treatment reflect the genotoxic stress induced. Our data suggest that VP, particularly in combination with irradiation, is associated with disruption of multiple survival pathways in chondrosarcoma cells, offering a promising avenue for therapeutic intervention. Future studies should investigate the interplay between autophagy, apoptosis, and Hippo signaling to enable their therapeutic targeting in cancer.
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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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