OVERCOMING COLORECTAL CANCER RESISTANCE TO 5-FLUOROURACIL BY TARGETING RAC1

KATIA OTTERSTEDT; FLORENCIA MALIZIA; LUCIA ZANOTTI; MACARENA MAMBERTO; NAHUEL CESATTI LALUCE; AVILA, AYLÉN; LUCIANO ANSELMINO; MAURICIO MENACHO MÁRQUEZ

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

Colorectal cancer (CRC) is the third most commonly diagnosedtype of cancer worldwide. 5-fluorouracil (5-FU) is a chemotherapy drug used in CRC treatment; however, half of CRCs are resistant to5-FU-based therapies. Rac1 is a key member of the Rho GTPasesfamily. Rac1 modulates cell adhesion and movement, and is highlyexpressed in tumors. Increasingly studies are reporting the role ofRac1 as a potential target for tumor therapy. The aim of this workwas to evaluate the impact of Rac1 in CRC resistance to therapy.In previous work, we identified genes and pathways associated withrecurrence after 5-FU-based therapies suggesting that Rac1 inhibition could be of benefit to overcome resistance. As approximately30–40% of CRCs carry a KRAS mutation, we began evaluating therelevance of RAC1 expression in KRAS wild-type/mutated CRCs.For this, we downloaded the TCGA-COAD dataset and separatedpatients according to RAC1 expression levels, determined using the“Survminer” package. In turn, we added an additional filter separating patients according to KRAS gene status. We found that high expression of RAC1 was associated with poor prognosis when KRASis mutated (p