Cristina Morelli, Vincenzo Formica, Silvia Riondino, Antonio Russo, Patrizia Ferroni*, Fiorella Guadagni and Mario Roselli Pages 3158 - 3172 ( 15 )
Objectives: The aim of the present review is to discuss the potential link between RAS, BRAF and microsatellite instability (MSI) mutational patterns and chemotherapeutic agent efficacy [Irinotecan (IRI) vs. Oxaliplatin (OXA)], and how this can potentially influence the choice of the chemotherapy backbone.
Methods: Following a review of the research literature, all pertinent articles published in the core journals were selected for the study. The inclusion criteria regarded relevant clinical and pre-clinical studies on the topic of interest (Relationship of OXA and IRI to KRAS/BRAF mutations and MSI).
Results: Excision repair cross complementation group 1 (ERCC1) expression is inhibited by KRAS mutation, making tumor cells more sensitive to OXA. Results from OPUS, COIN and PRIME trials support that no conclusive data are available for BRAF mutant population because of the small number of patients. Enhanced IRI cytotoxicity to MSI cell lines is due to the participation of some of the mismatch repair (MMR) components in various DNA repair processes and their role in the maintenance of the pro-apoptotic effect of IRI and G2/M cell arrest.
Conclusion: OXA and IRI are indispensable drugs for mCRC treatment and their selection must be as careful as that of targeted agents. We suggest taking into consideration the interaction between known genomic alterations and OXA and IRI activity to personalize chemotherapy in mCRC patients.
Oxaliplatin, irinotecan, colorectal cancer, chemotherapy, molecular targets, KRAS, BRAF, MSI.
Department of Systems Medicine, Medical Oncology Unit, Tor Vergata Clinical Center, Tor Vergata University of Rome, Viale Oxford 81, 00133, Rome, Department of Systems Medicine, Medical Oncology Unit, Tor Vergata Clinical Center, Tor Vergata University of Rome, Viale Oxford 81, 00133, Rome, Department of Systems Medicine, Medical Oncology Unit, Tor Vergata Clinical Center, Tor Vergata University of Rome, Viale Oxford 81, 00133, Rome, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Via del Vespro 129, 90127 Palermo, BioBIM (InterInstitutional Multidisciplinary Biobank), IRCCS San Raffaele Pisana, Via di Val Cannuta 247, 00166 Rome, BioBIM (InterInstitutional Multidisciplinary Biobank), IRCCS San Raffaele Pisana, Via di Val Cannuta 247, 00166 Rome, Department of Systems Medicine, Medical Oncology Unit, Tor Vergata Clinical Center, Tor Vergata University of Rome, Viale Oxford 81, 00133, Rome