Genetics of rectal cancer and novel therapies: primer for radiologists

Rectal cancer accounts for one-third of newly diagnosed colorectal cancer cases. Given its anatomical location and risk for local recurrence, a multidisciplinary treatment program including surgery, radiation therapy, and chemotherapy has demonstrated improved outcomes in localized disease. Genetic analysis has become part of the standard approach for management of advanced disease and new trials are considering tailored therapies for locally advanced disease. This review describes molecular subsets of colorectal cancer; implications for clinical management, including patterns of metastatic spread and response to therapies; and emerging matched therapies. During the last decade, significant biological differences have been noted based on colorectal cancer primary location and here we focus on rectal cancers and relevant markers for this disease. As more treatment for localized rectal cancer is shifted to the neoadjuvant setting and more targeted regimens are developed for metastatic disease, radiologists will increasingly see patients defined by molecular subsets and their awareness of the genetics of rectal cancer will help further refine our understanding of this disease.