Molecular Pathways and Cellular Metabolism in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is, for sporadic forms, most strongly related to lifestyle factors. The epidemic of obesity and physical inactivity has great impact on disease patterns. Likewise, an altered metabolism has consequences at the cellular and molecular level with implications for cancer initiation and growth. Understanding the genetic hallmarks of cancers has improved over the years and now also includes cancer metabolic reprogramming. The initiation of cancer through genetic instability, including chromosomal instability, microsatellite instability and epigenetic silencing through the CpG island methylator phenotype follows pathways with distinct clinical, pathological, and genetic characteristics. These can potentially be used for molecular classification and comprehensive tumor profiling for improved diagnostics, prognosis and treatment in CRC. For one, epidermal growth factor receptor-directed treatment now considerably prolongs survival in metastatic disease, but defining the true responders from non-responders has emerged as complex. Further, the use of both non-steroidal anti-inflammatory drugs including cyclooxygenase-2 inhibitors is associated with a decreased incidence of adenoma and reduced mortality rate of CRC. This review gives a brief yet updated overview of the current understanding of CRC as a genetic and molecular disease with potential for clinical pathways of prevention, improved prediction and better prognosis in the future.

The Sirtuin 3 Expression Profile Is Associated with Pathological and Clinical Outcomes in Colon Cancer Patients

“…Occurrence of colon cancer has been shown as a consequence of interaction between genetic predisposition and environmental factors, including epidemic obesity and sedentary lifestyle [33]. Combined effects from six individual factors, that is, dietary intake, alcohol consumption, smoking, physical activity, body mass index, and sleep patterns, have been associated with incidence of colon cancer in non-Western populations, whereas the Western dietary pattern has been found in association with CRC in non-Asian populations [34–37].…”

“…Stratification of risk factors was not performed in statistical analysis of this study due to sample size and the complexity of etiology in colon cancer, which is outside the scope of this paper. Even though development of colon cancer originates from stem cells and “mucosa at risk” through various pathways following different responses to DNA damage [33, 38–41], common outcomes are presented at the cellular and molecular level and manifested by several caner hallmarks and molecular characteristics [42–44]. …”

The biological complexity of colorectal cancer: insights into biomarkers for early detection and personalized care

“…More rarely, MSI has been divided into positive or negative, with MSI-L and MSS considered as a unique group [Domingo et al 2013;Simons et al 2013;Hagland et al 2013]. A panel of five mononucleotide markers (i.e.…”

Colorectal cancer subtypes: Translation to routine clinical pathology

“…Recently, KRAS mutations have been associated with metabolism in cancer cells [53]. In particular, it is well established that cancer cells undergo metabolic reprogramming to a glycolytic state to survive and maintain proliferation in a hostile environment and there is increasing evidence this warburg effect is promoted by oncogenes, including KRAS [53].…”

“…In particular, it is well established that cancer cells undergo metabolic reprogramming to a glycolytic state to survive and maintain proliferation in a hostile environment and there is increasing evidence this warburg effect is promoted by oncogenes, including KRAS [53]. In CRC, leptin production has been associated with adverse outcome in male patients, associating with advanced disease, nodal status and venous invasion [54].…”