Environmental exposures, tumor heterogeneity, and colorectal cancer outcomes

Considerable progress has been made in colorectal cancer (CRC) over the past two decades but it still remains the third commonest and third most deadly cancer in the USA. Epidemiologic and experimental studies have continued to describe links between environmental risk factors for developing nonhereditary CRC. However, the most significant recent advances have come through the understanding of CRC tumor heterogeneity and its impact on the variability of treatment efficacy. Using the KRAS mutation as a predictive biomarker for anti-epidermal growth factor receptor therapy is an example of how the genetic diversity of tumors can lead to a more individual or so-called personalized medicine with the goal of providing more benefits to patients, without unnecessary adverse side effects. Most recent reviews on this topic have focused on the key cancer pathways for which targeted therapies for CRC already exist. Less attention has recently been given to the three major genetic subtypes of CRC. Chromosomal instability, microsatellite instability, and CpG island methylator phenotype are thought to be the three major genetic and epigenetic alterations that drive tumorigenesis. In the past, these genetic alterations were used as a prognostic indicator, but recent data have demonstrated their correlation with treatment response.