Personalised use of repurposed non-anticancer drugs in colorectal cancer based on up-regulated signalling pathways: A real world cohort feasibility study.

833 Background: Targeting signaling pathways in colorectal cancers is a common therapeutic strategy. In addition to targeted drugs, non- anticancer drugs approved for use in other health conditions can inhibit key pathways. De novo tumor transcriptome analysis can identify patient-specific up- and down-regulated transcripts, based on which the corresponding repurposed drugs can be used in synergistic combinations with standard of care (SoC) regimens. Methods: This retrospective study was conducted on a real-world cohort of 459 colorectal cancer cases (218 females, 241 males; median age 56 years) who had taken Exacta multi-omics tumor profiling for selection of personalized treatments. Transcriptome analysis was performed as part of the evaluations to determine up and down-regulated gene transcripts for selecting targeted, endocrine, and cytotoxic anticancer agents as well as non-anticancer (repurposed) drugs and phytochemicals that could be used for tandem targeting of the dysregulated signaling pathways, as indicated in the table below. Results: Transcriptome analysis of this cohort revealed dysregulation of ≥1 pathway in 391 patients (85.2%). MAPKs (n = 244, 53.2%) and MMPs (n = 210, 45.8%) were most frequently upregulated. Celecoxib (n = 292, 63.6%), Atorvastatin (n = 255, 55.6%), and Doxycycline (n = 208, 45.3%) were the most frequently indicated repurposed drugs for targeting the identified dysregulated pathways. Potential indications for ≥1 repurposed drugs were seen in 353 patients (76.9%). Conclusions: Several cellular signaling pathways are known or potential therapeutic targets in cancers. The present study indicates that it may be possible to use multi-omics analyses to create personalized treatment strategies using a synergistic combination of repurposed drugs to potentiate the action of SoC systemic anticancer agents in colorectal cancer. Biomarkers for non anti-cancer drugs selection. Drug Biomarker/Gene Expression Aspirin PTGS2 (COX2) Atorvastatin HMGCR, MAPK Bromelain PTGS2 (COX2) Celecoxib PTGS2 (COX2), FZD, WNT, ΜΑΡΚ Chloroquine HMGB1 Curcumin MMP, BIRC5, BCL2 Doxycycline MMP Metformin MMP, BCL2, ΜΑΡΚ Quercetin FZD, WNT Resveratrol MMP, BCL2, PCNA, PTGS2 (COX2) Vitamin C SLC2A1 (GLUT1) Artesunate FZD, WNT, MMP, BCL2 Cannabidiol MMP Epigallocatechin gallate MMP, MAPK Mebendazole XIAP, MMP, MAPK