Abstract
Precision medicine is essential for the modern care of a patient with cancer. Comprehensive molecular profiling of the tumor itself is necessary to determine the presence or absence of certain targetable abnormalities or biomarkers. In particular, lung cancer is a disease for which targetable genomic alterations will soon guide therapy in the majority of cases. In this comprehensive review of solid tumor-based biomarkers, we describe the genomic alterations for which targeted agents have been approved by the United States Food and Drug Administration (FDA). While focusing on alterations leading to approvals in a tumor-agnostic fashion (MSI-h, TMB-h, NTRK) and on those alterations with approvals in multiple malignancies (BRAF, ERBB2, RET, BRCA, PD-L1), we also describe several biomarkers or indications that are likely to lead to an approved drug in the near future (e.g., KRAS G12C, PD-L1 amplification, HER2 overexpression in colon cancer, HER2 mutations in lung cancer). Finally, we detail the current landscape of additional actionable alterations (EGFR, ALK, ROS1, MET) in lung cancer, a biomarker-rich malignancy that has greatly benefitted from the precision oncology revolution.
Highlights
Precision medicine, defined as supplying the right treatment to the right patient at the right time, has become an essential element of cancer care, Taking advantage of novel technologies developed following sequencing of the human genome approximately twenty years ago, precision oncology leverages a tumor’s molecular features with available and novel therapeutics [1,2,3,4]
While larger cohorts and further study is needed into the molecular mechanisms of response [55], these findings suggest the site-agnostic model of immune checkpoint inhibitors (ICIs) use should be evaluated thoughtfully in these and other MSI-H/dMMR solid tumors when other treatment options exist [56]
Lung Cancer In June 2017, the Food and Drug Administration (FDA) approved the combination of dabrafenib and trametinib for metastatic non-small cell lung cancer (NSCLC) patients harboring BRAF V600E mutations based upon the international, multicenter, three-cohort, non-randomized, open-label BRF113928 trial [103,104,105]
Summary
Precision medicine, defined as supplying the right treatment to the right patient at the right time, has become an essential element of cancer care, Taking advantage of novel technologies developed following sequencing of the human genome approximately twenty years ago, precision oncology leverages a tumor’s molecular features with available and novel therapeutics [1,2,3,4]. Molecular profiling is available to comprehensively characterize a patient’s tumor within as few as two weeks and includes interrogation of anywhere from hundreds of genes to the whole exome for mutations, insertions, deletions or copy-number alterations via next-generation sequencing (NGS), gene fusions with RNA sequencing and various protein changes with IHC. The goal of such extensive testing is to unveil the genomic makeup of a patient’s tumor, which can inform the most effective therapeutic approach. NSCLC serves as a model for precision oncology where patients can benefit substantially from employment of molecular profiling
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