Biomarkers in precision therapy in colorectal cancer

Abstract

Colorectal cancer (CRC) is the most commonly diagnosed cancer in Europe. Because CRC is also a major cause of cancer-related deaths worldwide, a lot of research has been focused on the discovery and development of biomarkers to improve the diagnostic process and to predict treatment outcomes. Up till now only a few biomarkers are recommended by expert panels. Current TNM criteria, however, cause substantial under- and overtreatment of CRC patients. Consequently, there is a growing need for new and efficient biomarkers to ensure optimal treatment allocation. An ideal biomarker should be easily translated into clinical practice, to identify patients who can be spared from treatment or benefit from therapy, ultimately resulting in precision medicine in the future. In this review we aim to provide an overview of a number of frequently studied biomarkers in CRC and, at the same time, we will emphasize the challenges and controversies that withhold the clinical introduction of these biomarkers. We will discuss both prognostic and predictive markers of chemotherapy, aspirin therapy as well as overall therapy toxicity. Currently, only mutant KRAS, mutant BRAF, MSI and the Oncotype DX® Colon Cancer Assay are used in clinical practice. Other biomarker studies showed insufficient evidence to be introduced into clinical practice. Divergent patient selection criteria, absence of validation studies and a large number of single biomarker studies are possibly responsible. We therefore recommend that future studies focus on combining key markers, rather than analysing single markers, standardizing study protocols, and validate the results in independent study cohorts, followed by prospective clinical trials.

Multiplexed single cell protein expression analysis in solid tumours using a miniaturised microfluidic assay

“…It has been proposed previously that p53 expression can be used as a biomarker for prognostic outcomes in cancer patients, though studies are conflicting on its usefulness [34]. Although overexpression is commonly observed in 60-80% of colorectal carcinoma, few studies have shown any statistical significance between p53 overexpression and survival outcomes [35].…”

The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy (Review)

“…Several known mutations are considered to be associated with a poorer patient outcome and/or failure of response to a certain therapy (18). Patients with inactive TP53 mutations, for example, are at an increased risk of mortality compared with their counterparts, but this mutation does not appear to affect the outcome of chemotherapy (123).…”

“…Although TNM is currently the most common CRC staging system, and an important basis to determine the treatment method and assessing prognosis, it is not a reliable tool for prediction and prognosis. Particularly, CRC patients with similar histopathology may have completely different progression and outcome depending on their genetic and epigenetic background (18). Thus, understanding the molecular pathways underlying the initiation and development of CRC is essential to identify novel molecular biomarkers for diagnosis and prognosis, thereby improving the outcome.…”

Immunohistochemical Markers of Clinical Significance in Carcinoma of the Colon and Rectum

“…In the studies done correlating Ki-67 status and survival rates, it has been found that lower Ki-67 rate was associated with recurrence and lower patient survival. 10 In contrast from the management view, the rapidly proliferating tumours have been found to respond well to adjuvant therapy. The Ki-67 assessment before therapy could predict the effectiveness of the treatment, whereas the same after treatment could predict the disease free survival of patients.…”