Predictive and prognostic biomarkers for neoadjuvant chemoradiotherapy in locally advanced rectal cancer

• Biomarkers are needed to assess treatment response in locally advanced rectal cancer.
• Experimental markers include proteins involved in cell proliferation and apoptosis.
• There is no one biomarker currently that has robust clinical utility.
• Microarrays that can interrogate a tumour for multiple candidates have potential.
• Circulating tumour cells or nucleic acids are likely the way forward.

Locally advanced rectal cancer is regularly treated with trimodality therapy consisting of neoadjuvant chemoradiation, surgery and adjuvant chemotherapy. There is a need for biomarkers to assess treatment response, and aid in stratification of patient risk to adapt and personalise components of the therapy. Currently, pathological stage and tumour regression grade are used to assess response. Experimental markers include proteins involved in cell proliferation, apoptosis, angiogenesis, the epithelial to mesenchymal transition and microsatellite instability. As yet, no single marker is sufficiently robust to have clinical utility. Microarrays that screen a tumour for multiple promising candidate markers, gene expression and microRNA profiling will likely have higher yield and it is expected that a combination or panel of markers would prove most useful. Moving forward, utilising serial samples of circulating tumour cells or circulating nucleic acids can potentially allow us to demonstrate tumour heterogeneity, document mutational changes and subsequently measure treatment response.