Circulating Tumor DNA: The Dawn of a New Era in the Optimization of Chemotherapeutic Strategies for Metastatic Colo-Rectal Cancer Focusing on RAS Mutation

SIMPLE SUMMARY: Molecularly targeted therapies have greatly contributed to the development of colorectal cancer treatments. Genomic profiling to identify gene alterations is a rapidly developing field. Liquid biopsies have recently drawn considerable attention because they offer several advantages over tissue biopsies and can be used to detect several soluble factors, including circulating tumor DNA. In this review, we discuss the usefulness of analyzing circulating tumor DNA to design more personalized and effective cancer treatments and discuss several ongoing clinical trials that aim to evaluate its utility. Genomic profiling using circulating tumor DNA could be integrated into clinical strategies for cancer treatment in the near future. ABSTRACT: Genotyping of tumor tissues to assess RAS and BRAF V600E mutations enables us to select optimal molecularly targeted therapies when considering treatment strategies for patients with metastatic colorectal cancer. Tissue-based genetic testing is limited by the difficulty of performing repeated tests, due to the invasive nature of tissue biopsy, and by tumor heterogeneity, which can limit the usefulness of the information it yields. Liquid biopsy, represented by circulating tumor DNA (ctDNA), has attracted attention as a novel method for detecting genetic alterations. Liquid biopsies are more convenient and much less invasive than tissue biopsies and are useful for obtaining comprehensive genomic information on primary and metastatic tumors. Assessing ctDNA can help track genomic evolution and the status of alterations in genes such as RAS, which are sometimes altered following chemotherapy. In this review, we discuss the potential clinical applications of ctDNA, summarize clinical trials focusing on RAS, and present the future prospects of ctDNA analysis that could change daily clinical practice.