Abstract 349: Association of DNA damage response capacity with neoadjuvant chemoradiation response in locally advanced rectal cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2021-07, Vol.81 (13_Supplement), p.349-349
• Main Authors: Demidova, Elena V., Lesh, Randy W., Avkshtol, Vladimir, Einarson, Margret B., Golemis, Erica A., Arora, Sanjeevani, Meyer, Joshua E.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2021-349

Background: Locally advanced rectal cancer (RC) cases are ~60% of newly diagnosed RCs, with neoadjuvant chemoradiation therapy (nCRT) followed by surgery as the standard of care. While nCRT is highly toxic, it is also beneficial. Recent prospective trials reported that up to 59% locally advanced RC cases exhibit complete clinical response, suggesting these patients as ideal candidates for organ preservation. However, currently there is no biomarker to predict who will or will not benefit from nCRT. The goal of this study was to establish a predictive biomarker for benefit from nCRT, based on the hypothesis that inherent DNA damage response (DDR) capacity contributes to nCRT response in RC. Methods: To gain insight into inherent DDR capacity, we profiled primary peripheral blood lymphocytes (pPBLs) from RC patients by quantitative immunofluorescence, Luminex-multianalyte assay, and pPBL DNA whole exome sequencing (WES). RC patients analyzed were segregated by neoadjuvant rectal (NAR) score: NAR14, poor responders (PoRs), n=21; 1