Colorectal Cancer Biomarkers in the Era of Personalized Medicine

Abstract

The 5-year survival probability for patients with metastatic colorectal cancer has not drastically changed over the last several years, nor has the backbone chemotherapy in first-line disease. Nevertheless, newer targeted therapies and immunotherapies have been approved primarily in the refractory setting, which appears to benefit a small proportion of patients. Until recently, rat sarcoma (RAS) mutations remained the only genomic biomarker to assist with therapy selection in metastatic colorectal cancer. Next generation sequencing has unveiled many more potentially powerful predictive genomic markers of therapy response. Importantly, there are also clinical and physiologic predictive or prognostic biomarkers, such as tumor sidedness. Variations in germline pharmacogenomic biomarkers have demonstrated usefulness in determining response or risk of toxicity, which can be critical in defining dose intensity. This review outlines such biomarkers and summarizes their clinical implications on the treatment of colorectal cancer. It is critical that clinicians understand which biomarkers are clinically validated for use in practice and how to act on such test results.

Colon cancer therapy by focusing on colon cancer stem cells and their tumor microenvironment

“…In personalized medicine patient's personal history, proteomic and genomic profile/specific biomarkers are used for increasing the response to therapy. By using large scale omics technologies such as proteomics and transcriptomics as mentioned in CRC molecular subtypes, cancer scientists determine the predictive biomarkers of therapy response (Patel, Fong, & Jagosky, ). Therefore, these biomarkers can be used in better personalization of therapies and reduction of adverse effects of the drug.…”

“…It is noteworthy that most of the different types of CSCs have a few shared deregulated stemness signaling pathways and also cell surface markers; however, blocking these markers and pathways have not yet given effective treatment in different cancers (Makena, Ranjan, Thirumala, & Reddy, 2018). In this case, one suggested the reason is that CSCs from different cancers may have different mechanisms of drug resistance and therefore, each cancer type may need a unique therapy (Kozovska, Gabrisova, & Kucerova, 2014 (Patel, Fong, & Jagosky, 2019).…”

Variant classification in precision oncology

“…While the overall prevalence might be lower compared to the classic tumor types where the initial discoveries were made, one should be aware that the concept of a single pathognomonic genetic event has limitations, particularly when it comes to the interpretation of individual molecular data. Importantly, the role of pharmacogenomics, that is, determining drug response based on sequencing results, is becoming more important with accumulating evidence (e.g., in colorectal cancer) and may be more broadly incorporated in oncological decision making in the near future. A third emerging topic is specific germline aberrations that require genetic counseling.…”

Consensus molecular subtypes (CMS) in metastatic colorectal cancer - personalized medicine decision

“…[3][4][5] Pharmacogenomics' biomarkers such as dihydropyrimidine dehydrogenase, uridine diphosphate glucuronosyltransferase 1A1, excision repair cross complementing rodent repair deficiency complementation group 1, VEGF and thymidylate synthase are also important when planning the treatment and deciding on the type (to choose the alternative systemic therapy), appropriate combination (less toxic) and dosages (to adjust the dose to lower the frequency and grade of the adverse effects) of systemic therapy. 6 New knowledge about the molecular heterogeneity of CRC, the discovery of biomarkers as predictive factors for disease prognosis and response to systemic treatment, and thus personalized medicine in this field, have also significantly contributed to the prolonged survival rates of patients. Besides gene mutations, tumour stroma and immunity also play a very important role in response to the systemic treatment and the prognosis of the disease.…”