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Simple Summary: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Next-generation sequencing technologies have identified new candidate genes and deepened the knowledge of the molecular mechanisms underlying the progression of colonic adenomas towards CRC. The main genetic, epigenetic, and molecular alterations driving the onset and progression of CRC in both hereditary and sporadic settings have also been investigated. The evaluation of the CRC risk based on the molecular characterization of early pre-cancerous lesions may contribute to the development of targeted preventive strategies development, help define specific risk profiles, and identify patients who will benefit from targeted endoscopic surveillance. Colorectal cancer (CRC) develops through a multi-step process characterized by the acquisition of multiple somatic mutations in oncogenes and tumor-suppressor genes, epigenetic alterations and genomic instability. These events lead to the progression from precancerous lesions to advanced carcinomas. This process requires several years in a sporadic setting, while occurring at an early age and or faster in patients affected by hereditary CRC-predisposing syndromes. Since advanced CRC is largely untreatable or unresponsive to standard or targeted therapies, the endoscopic treatment of colonic lesions remains the most efficient CRC-preventive strategy. In this review, we discuss recent studies that have assessed the genetic alterations in early colorectal lesions in both hereditary and sporadic settings. Establishing the genetic profile of early colorectal lesions is a critical goal in the development of risk-based preventive strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: The number of interval colorectal cancers is an intermediate measure of the effectiveness of a population-screening programme in decreasing colorectal cancer mortality. Differences between interval and screen-detected cancers have been reported. Better characterization of colorectal cancer to differentiate false-negative faecal immunochemical test results from true interval cancers would help determine whether to focus more on the organizational aspects of a screening programme or on stratifying colorectal cancer risk. This review provides a comprehensive overview of the epidemiological, clinical, and molecular characteristics of interval colorectal cancers. Tumors that are not detected by screening tests are known as interval cancers and are diagnosed clinically after a negative result in the screening episode but before the next screening invitation. Clinical characteristics associated with interval colorectal cancers have been studied, but few molecular data are available that describe interval colorectal cancers. A better understanding of the clinical and biological characteristics associated with interval colorectal cancer may provide new insights into how to prevent this disease more effectively. This review aimed to summarize the current literature concerning interval colorectal cancer and its epidemiological, clinical, and molecular features. [ABSTRACT FROM AUTHOR]

Integrin α6β4 is one of the main laminin receptors and is primarily expressed by epithelial cells as an active component of hemidesmosomes. In this article, after a brief summary about integrins in the gut epithelium in general, I review the knowledge and clinical potential of this receptor in human colorectal cancer (CRC) cells. Most CRC cells overexpress both α6 and β4 subunits, in situ in primary tumours as well as in established CRC cell lines. The mechanisms that lead to overexpression have not yet been elucidated but clearly involve specific transcription factors such as MYC. From a functional point of view, one key element affecting CRC cell behaviour is the relocalization of α6β4 to the actin cytoskeleton, favouring a more migratory and anoikis-resistant phenotype. Another major element is its expression under various molecular forms that have the distinct ability to interact with ligands (α6β4 ± ctd) or to promote pro- or anti-proliferative properties (α6Aβ4 vs. α6Bβ4). The integrin α6β4 is thus involved in most steps susceptible to participation with CRC progression. The potential clinical significance of this integrin has begun to be investigated and recent studies have shown that ITGA6 and ITGB4 can be useful biomarkers for CRC early detection in a non-invasive assay and as a prognostic factor, respectively. [ABSTRACT FROM AUTHOR]