Molecular changes and associated acquired resistance of rectal tumors following chemoradiotherapy (CRT) have not been well studied. In this interview, Mohamed E. Salem, MD, Levine Cancer Institute, Charlotte, NC, discusses results of a paired analysis of pre-CRT biopsies and their respective post-CRT samples in rectal cancer patients. CRT was not found to alter microsatellite instability status or the level of tumor mutational burden. However, CRT did result in a gain of molecular alterations that may mediate resistance mechanisms or be predictive of relapse. This interview was recorded via an online conference call with The Video Journal of Oncology (VJOncology).