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Agnostic Biomarkers in Molecular Pathology
Zeynep Sagnak Yilmaz1,2, Yasemin Cakir1, Sibel Demir Kececi1,3
1Department of Molecular Pathology, Dokuz Eylül University Graduate School of Health Sciences, İzmir, Türkiye.
Journal of Clinical Practice and Research
|November 19, 2025
Summary
Tumor-agnostic therapies target specific molecular alterations, not cancer type. Approved biomarkers include MSI, NTRK, TMB, BRAF V600E, and RET fusions, with ongoing research for new targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Molecular alterations drive cancer cell behavior and are crucial for diagnosis and targeted therapy development.
- Identifying common targetable mutations across diverse tumor types has enabled the rise of tumor-agnostic therapies.
- Five biomarkers are currently approved for tumor-agnostic therapy: microsatellite instability (MSI), neurotrophic tyrosine receptor kinase (NTRK) fusions, tumor mutation burden (TMB), BRAF V600E mutation, and rearranged during transfection (RET) fusions.
Purpose of the Study:
- To review the current landscape of approved tumor-agnostic biomarkers and therapies.
- To highlight the significance of molecular alterations in guiding cancer treatment decisions.
- To discuss ongoing research into novel molecular targets for future agnostic therapies.
Main Methods:
- Literature review of FDA-approved tumor-agnostic biomarkers and therapies.
- Analysis of studies identifying common molecular alterations across various cancer types.
- Examination of ongoing research into potential new agnostic biomarkers.
Main Results:
- The FDA has approved specific therapies for MSI-high/TMB-high tumors (pembrolizumab), NTRK fusions (larotrectinib, entrectinib), BRAF V600E mutations (dabrafenib/trametinib), and RET fusions (selpercatinib).
- These approvals represent a significant milestone in personalized cancer treatment.
- The efficacy of agnostic therapy relies on identifying new, actionable biomarkers.
Conclusions:
- Tumor-agnostic therapies represent a paradigm shift in cancer treatment, focusing on molecular profiles rather than tumor origin.
- Continued research into biomarkers like PD-L1, KRAS, NRG1, FGFR, ALK, AKT, HER2, PIK3CA, and BRCA is essential for expanding agnostic treatment options.
- Identifying new agnostic biomarkers will enhance positive responses to these targeted therapies.
