Impact of tissue-agnostic approvals for patients with gastrointestinal malignancies

Gastrointestinal (GI) malignancies encompass a broad range of tumors with lim-ited 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 treat-ment 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 clin-ical 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.