Actionable Potentials of Less Frequently Mutated Genes in Colorectal Cancer and Their Roles in Precision Medicine

Abstract

Global statistics have placed colorectal cancer (CRC) as the third most frequently diagnosed cancer and the fourth principal cause of cancer-related deaths worldwide. Improving survival for CRC is as important as early detection. Personalized medicine is important in maximizing an individual’s treatment success and minimizing the risk of adverse reactions. Approaches in achieving personalized therapy in CRC have included analyses of specific genes with its clinical implications. Tumour genotyping via next-generation sequencing has become a standard practice to guide clinicians into predicting tumor behaviour, disease prognosis, and treatment response. Nevertheless, better prognostic markers are necessary to further stratify patients for personalized treatment plans. The discovery of new markers remains indispensable in providing the most effective chemotherapy in order to improve the outcomes of treatment and survival in CRC patients. This review aims to compile and discuss newly discovered, less frequently mutated genes in CRC. We also discuss how these mutations are being used to assist therapeutic decisions and their potential prospective clinical utilities. In addition, we will summarize the importance of profiling the large genomic rearrangements, gene amplification, and large deletions and how these alterations may assist in determining the best treatment option for CRC patients.

Microsatellite Instability in Colorectal Cancer Liquid Biopsy—Current Updates on Its Potential in Non-Invasive Detection, Prognosis and as a Predictive Marker

“…Previously, studies had proven implementation of biomarkers from blood as a non-invasive method for CRC screening, particularly during its early stages (stage I or premalignant stage) [ 63 , 64 , 65 , 66 , 67 ]. Examples of the markers evaluated were (1) proteins (hemoglobin) [ 68 , 69 , 70 , 71 ]; (2) deoxyribonucleic acid/DNA from intact cells or blood circulation (including methylation markers) [ 72 , 73 , 74 , 75 , 76 , 77 ]; (3) ribonucleic acid/RNA (messenger RNA, non-coding RNA and microRNA) [ 78 , 79 , 80 , 81 ]; (4) genes (mutation) [ 82 , 83 ]; and (5) low molecular weight metabolites (volatile organic compounds) [ 84 ]. Since the approval of first liquid biopsy-based test by the Food and Drug Administration (FDA) in 2016, numerous blood-based detection methods have been the focus of CRC screening to overcome the above-mentioned difficulties in traditional tissue biopsy testing [ 85 , 86 , 87 ].…”

Theoretical and in silico Analyses Reveal MYC as a Dynamic Network Biomarker in Colon and Rectal Cancer

“…A study on immunohistochemical staining for metastatic colorectal cancer found that patients with a high expression level of c-MYC had a significantly lower progression-free survival time and overall survival than those with reduced c-MYC expression (Strippoli et al, 2020). In summary, these findings indicate that the uncertain role of MYC function warrants further investigation (Yunos et al, 2020).…”

Analysis of Copy Number Variations in Solid Tumors Using a Next Generation Sequencing Custom Panel

“…Despite this fact and the relatively small size of our cohort, the spectrum of CNVs observed in our study was coincident with previous reports. Thus, ERRB2, MET, or EGFR amplifications were frequently found in CRC while FGFR1 and EGFR CNVs were present in a small but significant percentage of lung tumors [17][18][19][20].…”