The evolving landscape of tissue‐agnostic therapies in precision oncology

Abstract

Tumor‐agnostic therapies represent a paradigm shift in oncology by altering the traditional means of characterizing tumors based on their origin or location. Instead, they zero in on specific genetic anomalies responsible for fueling malignant growth. The watershed moment for tumor‐agnostic therapies arrived in 2017, with the US Food and Drug Administration's historic approval of pembrolizumab, an immune checkpoint inhibitor. This milestone marked the marriage of genomics and immunology fields, as an immunotherapeutic agent gained approval based on genomic biomarkers, specifically, microsatellite instability‐high or mismatch repair deficiency (dMMR). Subsequently, the approval of NTRK inhibitors, designed to combat NTRK gene fusions prevalent in various tumor types, including pediatric cancers and adult solid tumors, further underscored the potential of tumor‐agnostic therapies. The US Food and Drug Administration approvals of targeted therapies (BRAF V600E, RET fusion), immunotherapies (tumor mutational burden ≥10 mutations per megabase, dMMR) and an antibody‐drug conjugate (Her2‐positive–immunohistochemistry 3+ expression) with pan‐cancer efficacy have continued, offering newfound hope to patients grappling with advanced solid tumors that harbor particular biomarkers. In this comprehensive review, the authors delve into the expansive landscape of tissue‐agnostic targets and drugs, shedding light on the rationale underpinning this approach, the hurdles it faces, presently approved therapies, voices from the patient advocacy perspective, and the tantalizing prospects on the horizon. This is a welcome advance in oncology that transcends the boundaries of histology and location to provide personalized options.

Winners of the 2023 honor awards for excellence at the annual meeting of the Chinese Medical Association-Taipei: Part I

“…1 To successful transformation from conventional therapy to the novel/modern tumor-agnostic therapy (also known as pan-tumor or histology-independent therapy), 13 many modern technological tools, such as immunohistochemistry (IHC), 1 fluorescence in situ hybridization (FISH), 18 polymerase chain reaction (PCR), 1,19 next-generation sequencing (NGS), 5 and gene expression profiling (GEP), 18 to offer a more precise and tailored strategy to combat cancers by identifying the "more specific" or "more precise" molecules, such as tyrosine receptor kinase-TRK (Larotrectinib or entrectinib applied by NTRK gene fusion), PD-1, PD-L1, PD-L2 (pembrolizumab or dostarlimab according to presence of MSI-H [microsatellite instability high], dMMR, or TMB-H [tumor mutational burden high] ≥10 mut/Mb), BRAF (dabrafenib or trametinib indicated by BRAF V600E mutation [substitution of valine to glutamic acid at position 600 of the BRAF protein]), RET (rearranged during transfection, selpercatinib based on RET gene fusion), and HER2 (trastuzumab deruxtecan, based on HER2/neu overexpression) involved in cancer growth and survival and by producing bullets which can attack cancers directly. 20 As shown by the authors, 1 many of the aforementioned modern technologies have been applied to finish their works.…”