Macrolides for Cancer

Macrolides exert their antitumor effects through various mechanisms. Clarithromycin markedly reduced the incidence of mucosa-associated lymphoid tissue (MALT) lymphoma with Helicobacter pylori eradication. For cancer growth signals, clarithromycin and roxithromycin exhibit their antitumor effects by inhibiting the Raf to mitogen-activated protein-kinase pathway by acting on extracellular signal-regulated kinase and exhibit antitumor effects. Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, is effective against cancer by inhibiting the phosphatidylinositol-3 kinase/Akt/mTOR signaling pathway. Ivermectin has been shown to inhibit the Wnt/β-catenin signaling pathway and the Hippo signaling pathway. Regarding growth suppressor evasion, clarithromycin can have an antitumor effect by suppressing TGF-β in combination with other drugs. Regarding resisting cell death, clarithromycin, azithromycin, and ivermectin can induce apoptosis. Clarithromycin and azithromycin can have antitumor effects by acting on autophagy in combination with anticancer drugs. Ivermectin has been reported to induce pyroptosis. Clarithromycin, azithromycin, and ivermectin can have antiangiogenic effects. Ivermectin is expected to inhibit epithelial–mesenchymal transition. Ivermectin and clarithromycin have been reported effective in their action on reactive oxygen species. Erythromycin is effective in overcoming resistance to anticancer drugs and has synergistic effects with other drugs. In clinical trials, the efficacy of clarithromycin has been established as an eradication therapy for MALT lymphoma. Also, clarithromycin, in combination with lenalidomide and dexamethasone, is effective in multiple myeloma. Rapamycin is effective in renal cell carcinoma, neuroendocrine tumors, breast cancer, etc., and has been approved by the FDA. Macrolides, which have various antitumor effects, will be the subject of future research, especially in combination with other drugs.