Applications of macrocyclic molecules in cancer therapy: Target cancer development or overcome drug resistance

Abstract Cancer is a worldwide leading cause of cancer‐related death due to a lack of efficient disease control by drugs. With the increasing unmet needs in cancer treatment, developing novel effective cancer drugs is in great demand. Macrocyclic molecules represent a group of drug molecules with a cyclic skeleton which endows them with unique drug properties such as improved bioavailability, enhanced metabolic stability, increased binding affinity, and favorable pharmacokinetics parameters. The Food and Drug Administration (FDA) has approved a bunch of macrocyclic drugs to treat cancer patients. However, the importance of such molecules in cancer drug development remains underestimated. Recent studies support that macrocyclic molecules can also serve as an effective strategy to overcome drug resistance in cancer treatment, but is a lack of review. The purpose of this manuscript was to provide shreds of evidence on the applications of macrocyclic molecules for cancer therapy: (1) act as cancer drugs to target different proteins critical for cancer development; (2) act as cancer drugs to target resistant mutants of oncogenes to overcome drug resistance in targeted therapy. This review will help to attract more interest in developing macrocyclic drugs for cancer therapy and potentially provide more novel strategies to benefit cancer patients and society.