Focusing the management of rectal cancer

Abstract

Rectal cancer treatment has undergone major changes over the last 15 years with a focus on individualized care based around MRI assessment of the relationship of the tumour to the mesorectal fascia, improved surgical techniques and targeted use of pre-operative oncological therapies in patients with locally advanced disease. The recognition that some tumours responded completely to pre-operative chemoradiotherapy, and the selective use of a non-operative policy has led to a quest to further identify those patients and their tumour in whom this approach could be used, irrespective of MRI stage. With no clear patient factors identified, the tumour and its gene expression has become a target for research to identify individual single-nucleotide polymorphisms, which may indicate a response to specific treatment, or not. To date some agents have been identified and trialed, such as cetuximab, with individual tumours being assessed for response allowing directed treatment. The reviewed paper by Sebio and colleagues report a study that links polymorphisms in the DNA repair gene XRCC1 with response to neoadjuvant 5-Fluorouracil treatment in rectal cancer patients. However, genetic heterogeneity alone may not explain the variations of drug response and environmental factors may lead to epigenetic effects and therefore alter responses. Therefore whilst this study demonstrates the impact of different single nucleotide polymorphisms (SNPs), it is only one step forward, but perhaps a step in the right direction.

Keywords: Rectal cancer; genomics; single nucleotide polymorphisms (SNPs); tumor heterogeneity.