Riok1, A Novel Potential Target in MSI-High p53 Mutant Colorectal Cancer Cells

Area of Science:

• Oncology
• Genomics
• Pharmacology

Background:

• Colorectal cancer (CRC) exhibits significant clinical heterogeneity.
• Understanding molecular drivers is crucial for targeted therapeutics.
• Microsatellite instability (MSI) and p53 genotype influence CRC biology.

Purpose of the Study:

• To identify key biological processes and novel kinases in CRC subtypes.
• To investigate the role of RIOK1 in CRC, stratified by MSI, p53, and KRAS genotypes.
• To evaluate the efficacy of RIOK1 inhibition based on specific genetic profiles.

Main Methods:

• Integration of proteomics, bioinformatics, and in vitro cell proliferation assays.
• Stratification of CRC cell lines by microsatellite (MS) state and p53 genotype.
• Inclusion of KRAS genotype in the analysis of RIOK1 inhibition.

Main Results:

• MSI-High p53-WT CRC cells show active cell-cycle, RNA metabolism, and WNT signaling.
• MSI-High mutant p53 CRC cells exhibit hyperactivated signaling, DNA repair, and immune processes.
• RIOK1 inhibition efficacy is dependent on p53 and KRAS genotypes, with HCT 116 cells being most sensitive.

Conclusions:

• In silico approaches can identify novel kinases for CRC sub-populations.
• RIOK1 is a promising therapeutic target in specific MSI-High CRC subtypes.
• Clinical genomics, including p53 and KRAS status, is vital for predicting drug response.