Notably, activation of the NLRP3 inflammasome and the subsequent secretion of IL-1β in MDSCs after Gem and 5-FU treatments may dampen the antitumor efficacy of the two agents.318 5-FU exerted higher antitumor effects when combined with IL-1R antagonists (IL-1Ra) or NLRP3 inflammasome inhibitors in tumor-bearing mice.319,320 Further, the IRAFU study (NCT02090101) reported that 5-FU in combination with bevacizumab and anakinra had promising efficiency and good safety profile in metastatic colorectal cancer (mCRC) patients who had undergone chemotherapy and anti-angiogenic therapy.321. This evidence concerns the gene NLRP3 and metastatic colorectal cancer.