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Updated: Oct 10, 2025
Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
Published on: April 11, 2018
Impact of tissue-agnostic approvals for patients with sarcoma
Roberto Carmagnani Pestana1, Juliana Rodrigues Beal1, Amanda Parkes2
1Centro de Oncologia e Hematologia Família Dayan-Daycoval, Hospital Israelita Albert Einstein, São Paulo, Brazil.
Abstract:
Tissue-agnostic drug development is a major step forward in offering treatment options for rare tumors. Sarcomas are heterogeneous rare malignancies with more than 100 subtypes. Recent failure of Phase III trials, nonbiomarker-driven clinical trials, and rarity hamper developmental therapeutics in sarcomas. Since a 'one-size-fits-all' approach continues to be the standard of care, tissue-agnostic approvals assume significance in sarcomas. In this review, we focus on the clinical evidence of recent drug approvals for neurotrophic tyrosine receptor kinase (NTRK) fusion, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) phenotype, and tumor mutation burden-high (TMB-H) status in the context of sarcomas, and the future landscape of tissue-agnostic targets, such as rearranged during transfection (RET), fibroblast growth factor receptor (FGFR), and neuregulin-1 (NRG1).
Insights
Tissue-agnostic drug approvals offer new hope for rare sarcoma tumors. This review examines evidence for NTRK fusion, MSI-H/dMMR, and TMB-H targets, plus future tissue-agnostic therapies.
Area of Science:
- Oncology
- Translational Medicine
- Rare Cancers
Background:
- Sarcomas are rare, heterogeneous malignancies with over 100 subtypes.
- Therapeutic development in sarcomas is hindered by trial failures, non-biomarker-driven approaches, and rarity.
- Tissue-agnostic drug approvals are gaining significance due to the limitations of traditional, 'one-size-fits-all' treatments.
Purpose of the Study:
- To review clinical evidence for recent tissue-agnostic drug approvals in sarcomas.
- To explore the potential of emerging tissue-agnostic targets in sarcoma treatment.
Main Methods:
- Literature review of clinical evidence for approved tissue-agnostic therapies in sarcomas.
- Analysis of biomarkers including neurotrophic tyrosine receptor kinase (NTRK) fusions, microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) status, and tumor mutation burden-high (TMB-H).
- Exploration of future tissue-agnostic targets like rearranged during transfection (RET), fibroblast growth factor receptor (FGFR), and neuregulin-1 (NRG1).
Main Results:
- Clinical evidence supports approvals for NTRK fusion-positive, MSI-H/dMMR, and TMB-H sarcomas.
- These approvals represent significant progress in treating rare sarcoma subtypes.
Conclusions:
- Tissue-agnostic drug development is crucial for advancing sarcoma treatment options.
- Further research into novel targets like RET, FGFR, and NRG1 is warranted to expand therapeutic strategies for rare tumors.
