Epigenetica e cancro del colon-retto: limiti e prospettive

Colorectal cancer (CRC) is one of the most common cancers worldwide and the second leading cause of cancer-related mortality. The current screening strategies, albeit effective for improving clinical outcomes, are still plagued by poor adherence rate, especially in western countries. An increasing number of studies is hence focusing on identification of innovative circulating biomarkers. CRC develops from early premalignant lesions to full blown cancer via a multi-step process, involving a kaleidoscope of genetic mutations accumulating over time. Recent improvements of our understanding of CRC biology, coupled with notable advances in molecular technologies, have led to identify a number of epigenetic alterations involved in colorectal carcinogenesis. These essentially include epigenetic marks, the best characterized of which is hypermethylation of DNA promoters. To date, many studies have convincingly demonstrated the existence of an association between methylation status of certain genes and risk of cancer, thus supporting its possible assessment as a new putative biomarker. Although increasing efforts have been placed for validating methylation assays in serum or plasma specimens, many aspects remains challenging, such as the large number of factors modulating concordance between tissues and plasma methylation profiles. Only a complete understanding of all aspects influencing the possibility to detect epigenetic abnormalities in the bloodstream will permit achieving the goal of translating the so-called liquid biopsy from basic research into clinical practice.