Abstract
Locally advanced rectal cancer is currently treated with pre-operative radiochemotherapy (pRCT), but the response is not uniform. Identification of patients with higher likelihood of responding to pRCT is clinically relevant, as patients with resistant tumors could be spared exposure to radiation or DNA-damaging drugs that are associated with adverse side effects. To highlight predictive biomarkers of response to pRCT, a systematic search of PubMed was conducted with a combination of the following terms: “rectal”, “predictive”, “radiochemotherapy”, “neoadjuvant”, “response” and “biomarkers”. Genetic polymorphisms in epithelial growth factor receptor (EGFR) and thymidylate synthase (TS) genes, the expression of several markers, such as EGFR, bcl-2/bax and cyclooxygenase (COX)-2, and circulating biomarkers, such as serum carcinoembryonic antigen (CEA) level, are promising as predictor markers, but need to be further evaluated. The majority of the studies did not support the predictive value of p53, while the values of Ki-67, TS and p21 is still controversial. Gene expression profiles of thousands of genes using microarrays, microRNA studies and the search for new circulating molecules, such as human telomerase reverse transcriptase mRNA and cell-free DNA, are providing interesting results that might lead to the identification of new useful biomarkers. Evaluation of biomarkers in larger, prospective trials are required to guide therapeutic strategies.
Highlights
Colorectal cancer (CRC) is the third most common cancer in the world, with an estimated 72,090 new cases/year for males and 70,480 for females in the USA
The same findings were obtained using the cell-free DNA (cfDNA) integrity index. These findings suggest that cfDNA may be used as a non-invasive marker of tumor response in patients undergoing neoadjuvant treatment for rectal cancer
A neoadjuvant radiochemotherapy approach followed by total mesorectal excision has become the standard treatment for patients with locally advanced rectal cancer
Summary
Colorectal cancer (CRC) is the third most common cancer in the world, with an estimated 72,090 new cases/year for males and 70,480 for females in the USA. It is the third most common cause of cancer-related death, with an estimated 26,580 and 24,790 deaths/year for males and females, respectively [1]. The estimated incidence in Europe and Italy respectively is 333,330/51,686 with a mortality of 148,788/19,103 [2]. CRC is the result of genetic and epigenetic alterations that cause disorders in cell growth, differentiation and apoptosis, resulting in transformation of normal epithelium to adenocarcinoma [4]. The accumulation of molecular alterations in oncogenes (e.g., KRAS) and loss of oncosuppressor genes (e.g., APC, TP53) occurs with stepwise changes in morphology from a small adenomatous polyp to an invasive carcinoma [5,6,7]
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