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Impact of tissue-agnostic approvals for patients with gastrointestinal malignancies
Deepak Bhamidipati1, Vivek Subbiah2
1Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abstract:
Gastrointestinal (GI) malignancies encompass a broad range of tumors with limited treatment options, particularly for advanced disease. With the development and implementation of next-generation sequencing (NGS) in routine practice, molecular-targeting therapies have been increasingly incorporated into the treatment paradigm for various cancers. Several drugs have achieved tissue-agnostic regulatory approvals, which offer promising biomarker-driven therapy options for patients with advanced GI malignancies. In this review, we focus on the clinical evidence for recent drug approvals for neurotrophic tyrosine receptor kinase (NTRK) fusion, microsatellite instability-high (MSI-H) phenotype, tumor mutation burden-high (TMB-H), BRAF V600E, and rearranged during transfection (RET), in the context of GI malignancies. We also highlight the future landscape of tissue-agnostic targets, such as human epidermal growth factor receptor 2 (HER2)/neu, fibroblast growth factor receptor (FGFR), and neuregulin (NRG)-1.
Insights
Targeted therapies are revolutionizing gastrointestinal (GI) cancer treatment. This review covers approved tissue-agnostic drugs for GI malignancies based on biomarkers like NTRK fusions and MSI-H, and future targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastrointestinal (GI) malignancies present limited treatment options for advanced stages.
- Next-generation sequencing (NGS) enables molecular-targeting therapies in routine cancer care.
- Tissue-agnostic drug approvals offer biomarker-driven options for advanced GI cancers.
Purpose of the Study:
- To review clinical evidence for approved tissue-agnostic therapies in GI malignancies.
- To discuss specific biomarkers including NTRK fusion, MSI-H, TMB-H, BRAF V600E, and RET.
- To explore emerging tissue-agnostic targets for future GI cancer treatment.
Main Methods:
- Literature review of clinical evidence for approved targeted therapies.
- Focus on tissue-agnostic drug approvals in GI malignancies.
- Analysis of biomarkers driving treatment selection.
Main Results:
- Several drugs targeting NTRK fusions, MSI-H, TMB-H, BRAF V600E, and RET are approved for GI cancers.
- These approvals represent significant advances in biomarker-driven therapy.
- Future targets like HER2/neu, FGFR, and NRG-1 show promise.
Conclusions:
- Tissue-agnostic therapies are transforming GI cancer treatment paradigms.
- Biomarker identification is crucial for selecting effective targeted treatments.
- Ongoing research into novel targets will expand therapeutic options for GI malignancies.
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