Variations in genes regulating tumor-associated macrophages (TAMs)-related functions are significantly associated with clinical outcomes in patients with metastatic colorectal cancer (mCRC) treated with bevacizumab-containing chemotherapy, a new study published online ahead of print in the journal Annals of Oncology has shown.1

For the study, researchers analyzed genomic DNA from tumor samples of patients receiving bevacizumab plus FOLFIRI (fluorouracil, leucovorin, irinotecan) as first-line treatment. Researchers tested 12 functional single-nucleotide polymorphisms in the genes CCL2, CCR2, HRG, PIGF, NFKB1, TBK1, CCL18, and IRF3 for associations with clinical outcomes in 228 participants of the TRIBE trial. Results were then validated in 248 KRAS wild-type participants of the FIRE3 trial.

Results showed that TBK1 rs7486100 was significantly associated with overall survival in KRAS wild-type patients in univariate analysis and had a strong trend toward significance in multivariable analysis.

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In addition, researchers observed an association between the T allele and progression-free survival in bevacizumab-treated patients but not cetuximab-treated patients.

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The study also demonstrated associations between CCL2 rs4586, CCL18 rs14304, and IRF3 rs2304205 and progression-free survival in KRAS mutant patients.

“These results also suggest that some TAM-related gene variations may predict outcomes of bevacizumab treatment in KRAS status-dependent manner,” the authors concluded.


  1. Sumakawa Y, Stintzing S, Cao S, et al. Variations in genes regulating tumor-associated macrophages (TAMs) to predict outcomes of bevacizumab-based treatment in patients with metastatic colorectal cancer: results from TRIBE and FIRE3 trials [published online ahead of print September 28, 2015]. Ann Oncol. doi: 10.1093/annonc/mdv474.