Biomarkers in the development of individualized treatment regimens for colorectal cancer

Abstract

IntroductionColorectal cancer (CRC) is the third most common and second most deadly malignancy in the world with an estimated 1. 9 million cases and 0.9 million deaths in 2020. The 5-year overall survival for stage I disease is 92% compared to a dismal 11% in stage IV disease. At initial presentation, up to 35% of patients have metastatic colorectal cancer (mCRC), and 20–50% of stage II and III patients eventually progress to mCRC. These statistics imply both that there is a proportion of early stage patients who are not receiving adequate treatment and that we are not adequately treating mCRC patients.BodyTargeted therapies directed at CRC biomarkers are now commonly used in select mCRC patients. In addition to acting as direct targets, these biomarkers also could help stratify which patients receive adjuvant therapies and what types. This review discusses the role of RAS, microsatellite instability, HER2, consensus molecular subtypes and ctDNA/CTC in targeted therapy and adjuvant chemotherapy.DiscussionGiven the relatively high recurrence rate in early stage CRC patients as well as the continued poor survival in mCRC patients, additional work needs to be done beyond surgical management to limit recurrence and improve survival. Biomarkers offer both a potential target and a predictive method of stratifying patients to determine those who could benefit from adjuvant treatment.

Differential expression of angiogenesis-related genes ‘VEGF’ and ‘angiopoietin-1’ in metastatic and EMAST-positive colorectal cancer patients

“…Numerous signaling pathways are associated with angiogenesis, including VEGF-A, ANGPT-1, and ANGPT-2, which significantly contribute to tumor growth and metastasis by providing oxygen, nutrients, and a safe microenvironment for tumor cells 42 . The rapid progress in identifying cancer biomarkers has shown promise in equipping precision medicine with the most appropriate treatment options based on the individual’s unique biomarker profile 43 , 44 . In this regard, genomic instability, particularly MSI, exhibits a pivotal role in tumor initiation and malignancies, and there is emerging evidence that this biomarker can be defined as a promising prognostic biomarker for CRC patients 45 .…”

State-of-the-art cytometry in the search of novel biomarkers in digestive cancers

“…These tumours typically do not metastasise and show poor response to chemotherapy. Despite this, they have a better clinical course than MSS tumours because of the higher production of neoantigens, making them more susceptible to treatment with immunotherapy ( 32 ). Other therapeutic strategies focus on the MAPK pathway status.…”

“…RAS, which controls cells proliferation, is often mutated in CRC ( 33 ), and monoclonal antibodies (mAbs) anti-EFGR as cetuximab are typically used to stop the abnormal signalling. Other mAbs like encorafenib targets KRAF, which is usually mutated in CRC, and it is used when anti-EFGR are not effective, as it is downstream in the MAPK pathway ( 32 ). Focusing on liquid biopsies, several serum proteins such as carcinoembryonic antigen (CEA) are found in CRC.…”

Current Targeted Therapy for Metastatic Colorectal Cancer

“…Continued comprehensive understanding of mCRC pathology and molecular drivers, and developing novel therapeutic approaches are necessary to further refine the treatment of mCRC. While validated targets, including RAS, BRAF, TRK, and MSI/dMMR, are important to choose the correct therapeutic strategy for patients with mCRC [ 167 ]. This is because disclosure of additional targets may lead to the discovery of potential predictive biomarkers of treatment response and the correct selection of patients.…”