Prediction of Therapy Response in Colorectal Cancer

Division Of Basic Sciences - Nci

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Abstract

We have performed extensive gene expression analyses of primary rectal cancer either resistant or sensitive to neoadjuvant CRT. This study resulted in a list of 41 genes that robustly identifies patients with a complete pathological response. Functional analyses are now conducted to silence genes upregulated in resistant tumor to explore whether we could increase the fraction of patients that would show response. We have succeeded in establishing single cell derived cell lines from a treatment native rectal cancer. Exposing the single derived cell lines to CRT we could reveal an enormous degree in the spectrum of response. The cell lines were analyzed by RNA seq and some prominent pathways emerged in the resistant cell lines, including ILK and WNT signaling. In functional analyses we now target these pathways using CRISPR to explore whether they could be made more sensitive to CRT. We propose to expand such studies to a larger number of rectal cancers and have put forward an application to the DoD to use treatment native biopsies, propagate them in nude mice, establish single cell derived cell lines and organoids.