Colorectal Cancer Church, David N.; Midgley, Rachel Susannah; Kerr, David J.
Biotargets of Cancer in Current Clinical Practice,
03/2012
Book Chapter
Advances in cytotoxic and biological therapies for colorectal cancer (CRC) over the last decade have resulted in improved survival of patients with both localised and advanced disease. However, ...treatment is guided largely by pathological stage, and many patients who receive adjuvant or palliative chemotherapy fail to benefit, due to the inability of current criteria to predict outcome and response to treatment on an individual patient basis. The identification of prognostic and predictive biomarkers in CRC has therefore been the focus of substantial research, and these efforts are beginning to translate into meaningful improvements in patient care. Convincing evidence now indicates that patients with localised (stage IIa) disease and tumour microsatellite instability have good prognosis and can be spared adjuvant chemotherapy, while gene-expression signatures also show significant utility in predicting the risk of relapse following surgical resection. The demonstration that KRAS mutation predicts lack of response to anti-EGFR therapies represents a significant step towards the individualisation of treatment for patients with CRC and serves as a paradigm for biomarker discovery and validation within high-quality prospective clinical trials. Unfortunately, despite these high-profile successes, a large percentage of the CRC biomarker literature comprises small retrospective studies with a high probability of selection and publication bias. Though the advent of high-throughput platforms is likely to facilitate rapid, unbiased identification of tumour biomarkers, careful experimental design and validation is required to avoid these pitfalls and minimise the risk of spurious false-positive results.
In this chapter, we provide a precis of the current literature on biomarkers in CRC and highlight the challenges faced by the oncologic community in the incorporation of such markers into clinical practice.
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