IGF1R and metastatic colorectal cancer: For instance, manuka honey restored the ability of metastatic colorectal cancer first-line drug 5-fluorouracil to abrogate resistance to apoptosis of cancer stem-like cells derived from the HCT-116 colon adenocarcinoma cell line by a pleiotropic mechanism involving the downregulation of IGF-1, IGF-2, IGF-1R, as well as other inhibitors of apoptosis, such as: inhibitors of apoptosis protein (IAP) family members survivin, livin, and XIAP; and heat shock proteins HSP-27, HSP-60, and HSP-70 (47).