Tokunaga R, et al. - Among enrollees in three randomized clinical trials (TRIBE, MAVERICC, and FIRE-3), the link between AMP-activated protein kinase (AMPK) pathway-related single nucleotide polymorphisms (SNPs) and metastatic colorectal cancer (mCRC) clinical outcomes was examined. The participants were 884 patients with mCRC treated with FOLFIRI, mFOLFOX6, or FOLFOXIRI combined with bevacizumab or cetuximab as the first-line chemotherapy. Six treatment cohorts were analyzed. Significant associations of progression-free survival (PFS) and overall survival (OS), but not with tumor response (TR), with the AMPK pathway were found. For chemotherapy in mCRC, AMPK pathway-related SNPs could serve as predictors.