What question did this study set out to answer?

The aim is to identify genotype-specific treatment responses and resistance mechanisms in colorectal cancer.

Precision Combination Therapy Opportunities in Colorectal Cancer Through PDX Drug Screening

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The aim is to identify genotype-specific treatment responses and resistance mechanisms in colorectal cancer.
Conducted large-scale in vivo drug screening using 140 patient-derived xenograft models.
Applied standard-of-care agents including anti-EGFR and BRAF/EGFR inhibitors.
Utilized whole-exome sequencing, RNA sequencing, and Reverse Phase Protein Array for molecular profiling.
Performed integrated multi-omics analyses to assess biomarkers of response.
BRAF V600E models demonstrated a 40% disease control rate with improved outcomes using PI3K or MAPK co-targeting.
RAS/RAF wild-type models showed 100% response in treatment-naïve cases, dropping to 40% in pretreated ones.
KRAS G12C models achieved a 70% disease control rate when combined with various inhibitors.
Identified additional vulnerabilities like WEE1 and EZH2 sensitivity specific to KRAS G12C tumors.

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Large-scale in vivo drug screening reveals actionable vulnerabilities in colorectal cancer, suggesting improved treatment strategies.

Sorokin et al. (2026) studied this question.

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