The molecular basis of chemoradiosensitivity in rectal cancer:implications for personalized therapies

Preoperative chemoradiotherapy represents the standard treatment for patients with locally advanced rectal cancer. Unfortunately, the response of individual tumors to multimodal treatment is not uniform and ranges from complete response to complete resistance. This poses a particular problem for patients with a priori resistant tumors because they may be exposed to irradiation and chemotherapy, treatment regimens that are both expensive and at times toxic, without benefit. Accordingly, there is a strong need to establish molecular biomarkers that predict the response of an individual patient's tumor to multimodal treatment and that indicate treatment-associated toxicities prior to therapy. Such biomarkers may guide clinicians in choosing the best possible treatment for each individual patient. In addition, these biomarkers could be used to identify novel molecular targets and thereby assist in implementing novel strategies to sensitize a priori resistant tumors to multimodal treatment regimens. The aim of this review is to summarize recent findings about the molecular basis of treatment resistance and treatment toxicity in patients with rectal cancer. Whole-genome, as well as single-biomarker or multibiomarker, analyses and their potential implications will be highlighted. At the end, we will outline a future vision of rectal cancer treatment in the era of personalized medicine.