RARE DISEASE
Chordoma
Chordoma
Chordoma
Synonyms: Notochordal sarcoma
Synonyms: Notochordal sarcoma
Synonyms: Notochordal sarcoma
Drug discovery
3
drugs
With orphan designations
Overview
Chordoma is a rare malignant tumor arising from notochord remnants, typically occurring in the skull base, spine, or sacrum. It is locally aggressive, often recurs despite treatment, and can metastasize. Diagnosis involves imaging and histopathology, with management requiring multidisciplinary care. Current research focuses on molecular targets (e.g., brachyury) and immunotherapy [1][3][9][18].
Burden
Five-year survival: 50–65% (improves to 65–70% with complete resection) [14][16].
High recurrence (~50%) and metastasis rates (30–40%), often impacting neurologic function and quality of life [4][16][19].
Requires long-term surveillance and multidisciplinary care due to chronic morbidity [4][9][19].
Therapies
Surgery: En bloc resection with negative margins is preferred, though challenging due to proximity to critical structures [8][13].
Radiation: High-dose proton beam or carbon ion therapy improves local control post-surgery [13][14].
Systemic therapy: Tyrosine kinase inhibitors (e.g., imatinib, erlotinib) for advanced/metastatic disease; clinical trials exploring brachyury-targeted vaccines [3][18].
Categories: rare bone diseases, rare endocrine diseases, rare genetic diseases, rare neoplastic diseases
Research Papers
2,030 drug discovery papers about Chordoma, with 4 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,030 drug discovery papers about Chordoma, with 4 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-10 | The molecular landscape of chordoma: Current frontiers from multi-omics to artificial intelligence.
Chordoma is a rare and aggressive malignant bone tumor of the axial skeleton that has historically challenged clinicians due to its complex anatomical locations and a high recurrence rate of up to 85%. This review synthesizes the most recent advances in chordoma research and offers an overview of how multi-omics, advanced immunology, and artificial intelligence are reshaping the treatment paradigm. Central to its pathogenesis is the T-box transcription factor Brachyury, which this review highlights as both the pathognomonic diagnostic marker and the primary therapeutic vulnerability. Cutting-edge innovations targeting this driver include covalent small-molecule binders, targeted protein degradation, and peptide-centric CAR-T cells designed to attack the intracellular oncoprotein. The tumor immune microenvironment is functionally dynamic, and new dimensions in cellular therapy, such as dual-specific CAR constructs and NK-cell platforms, are being engineered to neutralize immunosuppressive factors. Beyond biological insights, the review emphasizes the role of computational biology, specifically how deep-learning and machine-learning models achieve expert-level precision in tumor segmentation and personalized survival forecasting. By integrating genomic, transcriptomic, epigenomic, and proteomic data, multiomics approaches can fully elucidate chordoma subtypes and underlying resistance mechanisms, ultimately paving the way for more precise and personalized therapeutic strategies.
2026-07-24 | Targeting chordoma via an isocitrate dehydrogenase-1-dependent susceptibility to redox metabolism.
Chordomas are rare cancers that arise along the axial skeleton. Alterations in metabolism are a hallmark of cancer, and we sought to identify metabolic vulnerabilities in chordoma. We discovered that the tricarboxylic acid (TCA)-related enzyme isocitrate dehydrogenase-1 (IDH1) was expressed highly in bulk and single-cell patient-derived chordomas and was associated with worse survival outcomes. IDH1 catalyzes the conversion of isocitrate and nicotinamide adenine dinucleotide phosphate (NADP+) to alpha-ketoglutarate (⍺-KG) and NADPH. This critical reaction influences TCA cycle metabolism, regulates epigenetic pathways, and affects redox balance. Both IDH1 knockdown and treatment with an inhibitor targeting IDH1 were toxic to chordoma cells. An integrated analysis of the transcriptomic, chromatin, and metabolomic responses on IDH1 inhibition converged on deregulated glutathione metabolism. IDH1 inhibition was associated with increased expression and enrichment of activating H3K27ac at NRF2 (nuclear factor erythroid 2-related factor 2) signature genes including those in the glutathione biosynthetic pathway. This was accompanied by reduction of both NADPH/NADP+ and reduced/oxidized glutathione (GSH/GSSG) ratios. Importantly, IDH1 inhibitor-driven toxicity was rescued via media supplementation with the antioxidant N-acetylcysteine, suggesting that IDH1 inhibition in chordomas creates a redox-dependent metabolic vulnerability. Finally, IDH1 inhibitor treatment reduced tumor growth in two independent chordoma mouse xenograft models. Our findings suggest a potential therapeutic avenue for further exploration in chordoma.
2026-07-21 | What are the current treatment options for sacral chordoma?
The primary treatment options for sacral chordoma include surgical resection and postoperative proton beam therapy, which improves local control and survival rates. Emerging targeted and immunotherapeutic approaches hold promise but require further validation.
2026-07-15 | Clinical challenges and therapeutic strategies in chordoma: Translating molecular insights into patient care.
Chordoma is a rare, locally aggressive bone tumor originating from notochordal remnants. Despite advances in surgical and radiation-based approaches, effective systemic therapies remain limited, and recurrence rates are high. This chapter explores the current clinical landscape of chordoma management with an emphasis on the integration of molecular insights into therapeutic decision-making. In particular, we highlight emerging strategies targeting brachyury and receptor tyrosine kinases, as well as promising immunotherapies, including PD-1/PD-L1 immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapies. We further underscore the pivotal role of institutional and multi-center biobanking efforts in enabling biomarker discovery, enhancing diagnostic accuracy, and facilitating patient prognostication. Alongside these efforts, clinical trial development and public health considerations provide a comprehensive overview of the present scope and future potential of precision medicine in chordoma. By emphasizing the translational potential of molecular profiling together with advances in the clinical, institutional, and public health infrastructures that support its implementation, this chapter outlines a pathway toward more personalized and effective care for patients with chordoma.
2026-07-14 | Progression-free survival 3 of 22 months achieved through third-line therapy with adebrelimab in patient with recurrent chordoma: a case report.
Lower cervical spine origin chordomas are exceedingly uncommon tumors, and treatment may present difficulties in particular areas of the cervical spine owing to its specific anatomic architecture and the interrelationship with the vertebral arteries, cervical nerve roots, and spinal cord. Due to its rarity, the mechanisms underlying tumorigenesis and optimal therapeutic strategies for recurrence remain poorly understood. A 57-year-old Chinese female with large vertebral and paravertebral lesions from C6 to T1 underwent surgically resection on Aug 13, 2018. The pathological diagnosis in the post-operative report was chordoma close to the resection margin. No adjuvant treatment was administered after surgery. The first recurrence occurred three years postoperatively and was associated with a high tumor burden. At that time, paraplegia (lower limb paralysis and involuntary urinary and fecal control disorders) occurred. This patient received apatinib tablets, a vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI), as first-line treatment. Second-line administration of a VEGFR-TKI anlotinib capsules and programmed death-1 (PD-1) inhibitor toripalimab injection; third-line administration of the programmed death-ligand 1 (PD-L1) inhibitor adebrelimab injection, resulted in a progression-free survival 3 of 22 months and an overall survival of 7.5 years. To the best of our knowledge, this represents the first reported case of adebrelimab use in immunotherapy for chordoma.
2026-08-10 | The molecular landscape of chordoma: Current frontiers from multi-omics to artificial intelligence.
Chordoma is a rare and aggressive malignant bone tumor of the axial skeleton that has historically challenged clinicians due to its complex anatomical locations and a high recurrence rate of up to 85%. This review synthesizes the most recent advances in chordoma research and offers an overview of how multi-omics, advanced immunology, and artificial intelligence are reshaping the treatment paradigm. Central to its pathogenesis is the T-box transcription factor Brachyury, which this review highlights as both the pathognomonic diagnostic marker and the primary therapeutic vulnerability. Cutting-edge innovations targeting this driver include covalent small-molecule binders, targeted protein degradation, and peptide-centric CAR-T cells designed to attack the intracellular oncoprotein. The tumor immune microenvironment is functionally dynamic, and new dimensions in cellular therapy, such as dual-specific CAR constructs and NK-cell platforms, are being engineered to neutralize immunosuppressive factors. Beyond biological insights, the review emphasizes the role of computational biology, specifically how deep-learning and machine-learning models achieve expert-level precision in tumor segmentation and personalized survival forecasting. By integrating genomic, transcriptomic, epigenomic, and proteomic data, multiomics approaches can fully elucidate chordoma subtypes and underlying resistance mechanisms, ultimately paving the way for more precise and personalized therapeutic strategies.
2026-07-24 | Targeting chordoma via an isocitrate dehydrogenase-1-dependent susceptibility to redox metabolism.
Chordomas are rare cancers that arise along the axial skeleton. Alterations in metabolism are a hallmark of cancer, and we sought to identify metabolic vulnerabilities in chordoma. We discovered that the tricarboxylic acid (TCA)-related enzyme isocitrate dehydrogenase-1 (IDH1) was expressed highly in bulk and single-cell patient-derived chordomas and was associated with worse survival outcomes. IDH1 catalyzes the conversion of isocitrate and nicotinamide adenine dinucleotide phosphate (NADP+) to alpha-ketoglutarate (⍺-KG) and NADPH. This critical reaction influences TCA cycle metabolism, regulates epigenetic pathways, and affects redox balance. Both IDH1 knockdown and treatment with an inhibitor targeting IDH1 were toxic to chordoma cells. An integrated analysis of the transcriptomic, chromatin, and metabolomic responses on IDH1 inhibition converged on deregulated glutathione metabolism. IDH1 inhibition was associated with increased expression and enrichment of activating H3K27ac at NRF2 (nuclear factor erythroid 2-related factor 2) signature genes including those in the glutathione biosynthetic pathway. This was accompanied by reduction of both NADPH/NADP+ and reduced/oxidized glutathione (GSH/GSSG) ratios. Importantly, IDH1 inhibitor-driven toxicity was rescued via media supplementation with the antioxidant N-acetylcysteine, suggesting that IDH1 inhibition in chordomas creates a redox-dependent metabolic vulnerability. Finally, IDH1 inhibitor treatment reduced tumor growth in two independent chordoma mouse xenograft models. Our findings suggest a potential therapeutic avenue for further exploration in chordoma.
2026-07-21 | What are the current treatment options for sacral chordoma?
The primary treatment options for sacral chordoma include surgical resection and postoperative proton beam therapy, which improves local control and survival rates. Emerging targeted and immunotherapeutic approaches hold promise but require further validation.
2026-07-15 | Clinical challenges and therapeutic strategies in chordoma: Translating molecular insights into patient care.
Chordoma is a rare, locally aggressive bone tumor originating from notochordal remnants. Despite advances in surgical and radiation-based approaches, effective systemic therapies remain limited, and recurrence rates are high. This chapter explores the current clinical landscape of chordoma management with an emphasis on the integration of molecular insights into therapeutic decision-making. In particular, we highlight emerging strategies targeting brachyury and receptor tyrosine kinases, as well as promising immunotherapies, including PD-1/PD-L1 immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapies. We further underscore the pivotal role of institutional and multi-center biobanking efforts in enabling biomarker discovery, enhancing diagnostic accuracy, and facilitating patient prognostication. Alongside these efforts, clinical trial development and public health considerations provide a comprehensive overview of the present scope and future potential of precision medicine in chordoma. By emphasizing the translational potential of molecular profiling together with advances in the clinical, institutional, and public health infrastructures that support its implementation, this chapter outlines a pathway toward more personalized and effective care for patients with chordoma.
2026-07-14 | Progression-free survival 3 of 22 months achieved through third-line therapy with adebrelimab in patient with recurrent chordoma: a case report.
Lower cervical spine origin chordomas are exceedingly uncommon tumors, and treatment may present difficulties in particular areas of the cervical spine owing to its specific anatomic architecture and the interrelationship with the vertebral arteries, cervical nerve roots, and spinal cord. Due to its rarity, the mechanisms underlying tumorigenesis and optimal therapeutic strategies for recurrence remain poorly understood. A 57-year-old Chinese female with large vertebral and paravertebral lesions from C6 to T1 underwent surgically resection on Aug 13, 2018. The pathological diagnosis in the post-operative report was chordoma close to the resection margin. No adjuvant treatment was administered after surgery. The first recurrence occurred three years postoperatively and was associated with a high tumor burden. At that time, paraplegia (lower limb paralysis and involuntary urinary and fecal control disorders) occurred. This patient received apatinib tablets, a vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI), as first-line treatment. Second-line administration of a VEGFR-TKI anlotinib capsules and programmed death-1 (PD-1) inhibitor toripalimab injection; third-line administration of the programmed death-ligand 1 (PD-L1) inhibitor adebrelimab injection, resulted in a progression-free survival 3 of 22 months and an overall survival of 7.5 years. To the best of our knowledge, this represents the first reported case of adebrelimab use in immunotherapy for chordoma.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
3 orphan drug designations for Chordoma.
3 orphan drug designations for Chordoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
afatanib and palbociclib | small molecules | FDA | 2020-11-12 | — | Collaborations Pharmaceuticals, Inc |
tazemetostat | small molecules | FDA | 2018-05-23 | — | Epizyme, Inc. |
BN-Brachyury; a heterologous prime/boost therapeutic cancer vaccine composed of MVA-BN-Brachyury (prime) and FPV-Brachyury (boost) | vaccines | FDA | 2018-04-30 | — | Bavarian Nordic A/S |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.