RAS Mutational Status in Advanced Colorectal Adenocarcinoma Treated With Anti-angiogenics: Preliminary Experience With Liquid Biopsy

To determinate molecular changes in the downstream epidermal growth factor receptor signaling pathway using serial liquid biopsies in patients with metastatic colorectal tumors (mCRC) under anti-angiogenic treatment. Determination of RAS mutation in primary tissue samples from colorectal tumors was performed in the 23 patients included in the study at diagnosis using quantitative-polymerase chain reaction. Sequential mutations were studied in circulating tumor (ct) DNA obtained from plasma samples. Twenty-three patients with RAS-mutated primary tumors were included. In the first ctDNA determination, 17 of these patients were found to have wild-type RAS status. Remarkably, three out of these 17 wild-type cases changed to RAS-mutated in subsequent ctDNA assays. Serial liquid biopsies in patients with mCRC might be a useful tool for identifying changes in the RAS mutation status in patients who had undergone previous anti-angiogenic therapy. The understanding of these changes might help to better define the landscape of mCRC and be the path to future randomized studies.