The Many Faces of Colorectal Cancer

Abstract

Colorectal cancer (CRC) is one of the most intensively studied cancer types, partly because of its high prevalence but also because of the existence of adenomatous precursor lesions, removal of which would prevent most cases of CRC from developing. Morphological steps in the evolution of these precursor lesions have been elucidated at a molecular level, and the adenoma–carcinoma sequence, as this has become known, is one of the classical examples of stepwise progression of cancer. Gaining this knowledge has been facilitated by the occurrence of a variety of forms of familial intestinal cancer, the molecular genetic background of which has been largely clarified. Apart from early detection of familial forms of CRC and its use in genetic counseling, until recently, this knowledge has had little impact on the clinical management of CRC. Classical clinicopathological parameters remain the essential parameters determining how a colorectal patient will be treated. This has dramatically changed in the last 5 years. With drugs specifically targeting the epidermal growth factor receptor (EGFR) having been shown effective in CRC, mechanisms responsible for resistance have been explored. The finding that KRAS-mutated cancers do not respond to anti-EGFR treatment has had a profound impact on clinical management and on molecular diagnostics of CRC. Understanding of the molecular pathogenesis of CRC has been instrumental in designing new approaches for therapy and translating it into molecular diagnostics, which contributes to the clinical management of CRC.