Abstract
Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and is heterogeneous both morphologically and molecularly. In an era of personalized medicine, the greatest challenge is to predict individual response to therapy and distinguish patients likely to be cured with surgical resection of tumors and systemic therapy from those resistant or non-responsive to treatment. Patients would avoid futile treatments, including clinical trial regimes and ultimately this would prevent under- and over-treatment and reduce unnecessary adverse side effects. In this review, the potential of specific biomarkers will be explored to address two key questions—1) Can the prognosis of patients that will fare well or poorly be determined beyond currently recognized prognostic indicators? and 2) Can an individual patient’s response to therapy be predicted and those who will most likely benefit from treatment/s be identified? Identifying and validating key prognostic and predictive biomarkers and an understanding of the underlying mechanisms of drug resistance and toxicity in CRC are important steps in order to personalize treatment. This review addresses recent data on biological prognostic and predictive biomarkers in CRC. In addition, patient cohorts most likely to benefit from currently available systemic treatments and/or targeted therapies are discussed in this review.
Highlights
Colorectal cancer (CRC) represents the third most common cancer in developed countries and is a leading cause of cancer deaths worldwide [1], highlighting the need to study predictive markers for response to available and emerging therapies
A recent study by Holch and colleagues investigated the prognostic and predictive relevance of primary tumor location. Their meta-analysis of first line clinical trials concluded that patients with left-sided RASWT metastatic CRC (mCRC) had significantly greater survival benefit from anti-epidermal growth factor receptor (EGFR) treatment compared with anti-vascular endothelial growth factor (VEGF) treatment when added to standard chemotherapy (HR, 0.71; 95% CI, 0.58–0.85; p = 0.0003)
There is some evidence to suggest that low expression of thymidylate synthase (TYMS) and EGFR is associated with increased tumor regression rates [87,88,89,90,91] and low p21 expression may be associated with improved survival in rectal cancer [92] (Table 2)
Summary
Colorectal cancer (CRC) represents the third most common cancer in developed countries and is a leading cause of cancer deaths worldwide [1], highlighting the need to study predictive markers for response to available and emerging therapies. The evolving understanding of the genetic heterogeneity of CRC suggests that a purely pathologic classification is insufficient to determine optimal therapy. Cancers 2020, 12, 812 events leading to adenoma and carcinoma formation is well described [2].
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