Importance of energy metabolism, angiogenesis and DNA repair in regulating neoadjuvant radiosensitivity in oesophageal and rectal adenocarcinoma

Abstract

Oesophageal and rectal adenocarcinoma are treated with neoadjuvant chemoradiotherapy in order to reduce tumour size prior to surgery, however only 10- 30% of patients have a complete pathological response and there are no clear biomarkers to indicate which patients will respond. Radioresistant tumours have altered metabolism and high rates of angiogenesis and DNA repair, biological processes which are closely interlinked. We tested the ability of 11B, our novel anti-angiogenic agent, and its structural analogues CC11, ZHCI and CCS to affect these biological processes. We used an isogenic model of oesophageal adenocarcinoma: OE33P (radiosensitive) and OE33R (radioresistant) cells and a radioresistant colorectal cancer cell line, HT29-LUC. We also used ex vivo explant and in vivo oesophageal and rectal adenocarcinoma treatment-naive tissue.