Published online Jul 7, 2016. doi: 10.3748/wjg.v22.i25.5668
Peer-review started: March 22, 2016
First decision: May 12, 2016
Revised: May 20, 2016
Accepted: June 13, 2016
Article in press: June 13, 2016
Published online: July 7, 2016
Improvements in screening and preventive measures have led to an increased detection of early stage colorectal cancers (CRC) where patients undergo treatment with a curative intent. Despite these efforts, a high proportion of patients are diagnosed with advanced stage disease that is associated with poor outcomes, as CRC remains one of the leading causes of cancer-related deaths in the world. The development of next generation sequencing and collaborative multi-institutional efforts to characterize the cancer genome has afforded us with a comprehensive assessment of the genomic makeup present in CRC. This knowledge has translated into understanding the prognostic role of various tumor somatic variants in this disease. Additionally, the awareness of the genomic alterations present in CRC has resulted in an improvement in patient outcomes, largely due to better selection of personalized therapies based on an individual’s tumor genomic makeup. The benefit of various treatments is often limited, where recent studies assessing the genomic diversity in CRC have identified the development of secondary tumor somatic variants that likely contribute to acquired treatment resistance. These studies have begun to alter the landscape of treatment for CRC that include investigating novel targeted therapies, assessing the role of immunotherapy and prospective, dynamic assessment of changes in tumor genomic alterations that occur during the treatment of CRC.
Core tip: Tumor somatic variants have a prognostic role, in addition to treatment selection in patients with solid tumor malignancies, including colorectal cancer (CRC). The application of this knowledge in the development of novel, targeted therapies has resulted in improved patient outcomes in this disease. Our objective is to provide an overview of the genomic alterations present in CRC and its role in treatment implications, in addition to providing an overview of ongoing and future clinical trials.