Plasma-Based Genotyping in Advanced Solid Tumors: A Comprehensive Review

SIMPLE SUMMARY: Targeted therapy is at the forefront of cancer diagnosis and treatment today for multiple advanced tumors. Although molecular testing of tumour tissue biopsies remains the gold standard for molecular diagnosis, it has certain limitations. There have been major advances in the use of plasma, also referred to as a “liquid biopsy,” to identify changes in the genome associated with approved targeted therapies. Here, we review key studies that have led to these approvals and a paradigm shift toward greater use of liquid biopsy in precision oncology. ABSTRACT: Molecular genotyping for advanced solid malignancies has transformed the clinical management of patients with metastatic disease. Treatment decisions in a growing number of tumors require knowledge of molecularly driven alterations in order to select optimal targeted therapy. Although genomic testing of tumor tissue is the gold standard for identifying targetable genomic alterations, biopsy samples are often limited or difficult to access. This has paved the way for the development of plasma-based approaches for genomic profiling. Recent advances in the detection of plasma-circulating tumor DNA (ctDNA) have enabled the integration of plasma-based molecular profiling into clinical practice as an alternative or complementary tool for genomic testing in the setting of advanced cancer, to facilitate the identification of driver mutations to guide initial treatment and diagnose resistance. Several guidelines now recommend the use of plasma where tumor tissue is limited to identify a targetable genomic alteration. Current plasma-based assays can evaluate multiple genes in comprehensive panels, and their application in advanced disease will be increasingly incorporated into standard practice. This review focuses on current and future applications of plasma ctDNA-based assays in advanced solid malignancies, while highlighting some limitations in implementing this technology into clinical practice.