Precision medicine in oncology involves identifying genomic alterations and other biomarkers that might predict response or resistance to therapies. This approach is a departure from the "blanket" approach to cancer treatment with the traditional methods of radiation, chemotherapy, and surgery. Targeted treatments for patients with specific genetic mutations represent some of the most significant developments in cancer research.
Patients with advanced (metastatic) solid tumors are the most appropriate candidates for genomic biomarker testing. Contemporary guidance and regulatory approvals support routine use of comprehensive, multigene next-generation sequencing mainly in metastatic solid tumors, rather than for most early-stage tumors or other cancers with established standard therapies. Historically, biomarker testing focused on unresectable cancers.
Learn more about soft tissue tumors.
Non-small cell lung cancer (NSCLC) requires a testing panel of more than five biomarkers at the time of diagnosis. In fact, current data suggest testing at least seven biomarkers during initial evaluation. The evolution of the treatment landscape for NSCLC marks a shift in precision medicine. Historically, platinum-based doublets were chosen for every patient; today, patients with metastatic NSCLC should undergo molecular testing at diagnosis to determine whether targeted therapy or immunotherapy is appropriate.
Small cell lung cancer, breast cancer, and thyroid cancer typically do not require a testing panel of more than five biomarkers at the time of diagnosis.
Learn more about molecular testing in NSCLC.
BRAF V600E therapy, including FDA-approved BRAF- and MEK-inhibitor combinations, is the standard of care for BRAF V600-mutant metastatic melanoma, with certain BRAF V600E indications later expanding to additional tumor types in specific medication labels.
Epidermal growth factor (EGFR) L858R is a well-established sensitizing EGFR mutation with FDA-approved EGFR TKIs specifically for NSCLC. In contrast, ATM-targeted poly(ADP-ribose) polymerase strategies and the use of BRAF/MEK inhibitors for non-V600 BRAF variants (eg, L597) remain investigational and are supported mainly by small case series and early-phase trials rather than large FDA tumor-agnostic approvals.
Learn more about practice essentials in melanoma.
Genomic heterogeneity has been demonstrated between primary and metastatic lesions, among different metastatic lesions, and even within regions of the same lesion. Therefore, liquid biopsy may provide a more comprehensive view of tumor genomics, reduce the need for invasive tissue biopsies, help predict treatment response or resistance, and support more frequent monitoring.
RAS mutations in colorectal cancer are early, truncal events; therefore, actionable information regarding the use of anti-EGFR antibodies in the metastatic setting can be found in the primary tumor. ESR1 mutations, which confer resistance to aromatase inhibitors in breast cancer, appear to occur most frequently during exposure to aromatase inhibitors but can also be present in primary tumors.
Learn more about colon cancer treatment.
Certain genetic mutations can significantly alter the choice of treatment; in some cases, they can signal that a cancer is more likely to become resistant to a treatment. For instance, in colorectal cancers, KRAS mutations might signal that a patient will not respond to certain drugs targeting the EGFR pathway.
MSH6 mutations are associated with Lynch syndrome and mismatch-repair deficiency, but they do not predict resistance to EGFR-targeted therapy. Similarly, IDH2 mutations have been identified in colorectal cancer at low frequencies and generally have not been associated with resistance to drugs targeting the EGFR pathway in this setting. The SF3B1 mutation is more commonly associated with hematological diseases than colorectal cancer.
Learn more about targeting KRAS in colorectal cancer.
Editor's Note: This article was created using several editorial tools, including generative AI models, as part of the process. Human review and editing of this content were performed prior to publication.
