Identification of 5-fluorouracil resistance reversing compounds by computational drug repositioning for colorectal cancer treatment

ANSELMINO, LUCIANO; MENACHO-MÁRQUEZ, MAURICIO

Congreso; Reunión Conjunta SAIC. SAI. AAFE. NANOMED-AR; 2021

Computational drug repositioning consists of the use of differentbioinformatics algorithms to identify known compounds that maybe candidates for treating a new pathology. In this work we usedthe Recursive Feature Elimination algorithm (RFE) to select a setof genes associated with tumour recurrence condition after 5-fluo-rouracil (5-FU) based chemotherapy in a group of colorectal cancer(CRC) patients. In combination, we used the RankProd algorithm,to filter the selected genes that were also differentially expressed(FDR>0,05). The list of genes was entered in the Library of Integrat-ed Network-Based Cellular Signatures (LINCS) database to identifythose compounds with the greatest probability to reverse the resis-tance-associated gene expression profile obtained.Among the proposed candidate drugs, we selected irinotecan (anti-neoplastic), ivermectin (antiparasitic) and amitriptyline (antidepres-sant). By MTT-based proliferation assays evaluated their effect onthe proliferation capacity on 5-FU sensitive and resistant CRC celllines.We found that both drugs further reduced the proliferation of 5-FUresistant CRC cells (P<0,05). Our preliminary results suggest thativermectin and amitriptyline have a potential 5-FU resistance rever-sal effect which have yet to be studied