Molecular biomarkers as predictors of response to neoadjuvant chemoradiation therapy in rectal cancer

The standard management of locally advanced rectal cancer includes neoadjuvant chemoradiation therapy (CRT) with 5-fluorouracil (5-FU) and concurrent pelvic irradiation (RT) to 45-50.4 Gy. This regimen results in downstaging in approximately 60% of patients and a pathological complete response (pCR) in 20%. Response to CRT is associated with improved rates of survival, local control, and sphincter preservation. However, some tumors are completely resistant to CRT; thus, non-responding patients experience only the toxicity of this treatment without any of its benefits. The ability to predict an individual patient's response to CRT would enable delivery of more effective treatment: patients predicted to respond would be directed to undergo CRT, while those predicted not to respond would be guided to alternative therapies or primary surgical resection. Molecular biomarkers have significant potential for predicting tumor regression. Furthermore, they may represent novel targets for therapeutic agents. Many studies have yielded promising results; to date, however, they have often lacked reproducibility. This review aims to summarize our current understanding of molecular biomarkers that may be used to predict response to CRT in rectal cancer.