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
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.