Antimicrobial peptides (AMPs) are a class of peptides found across a wide array of organisms
that play key roles in host defense. AMPs induce selective death in target cells and orchestrate specific or
nonspecific immune responses. Many AMPs exhibit native anticancer activity in addition to antibacterial
activity, and others have been engineered as antineoplastic agents. We discuss the use of AMPs in the detection
and treatment of cancer as well as mechanisms of AMP-induced cell death. We present key examples
of cathelicidins and transferrins, which are major AMP families. Further, we discuss the critical roles
of protein-protein interactions (PPIs) in cancer and how AMPs are well-suited to target PPIs based on
their unique drug-like properties not exhibited by small molecules or antibodies. While peptides, including
AMPs, can have limited stability and bioavailability, these issues can be overcome by peptide backbone
modification or cyclization (e.g., stapling) and by the use of delivery systems such as cellpenetrating
peptides (CPPs), respectively. We discuss approaches for optimizing drug properties of peptide
and peptidomimetic leads (modified peptides), providing examples of promising techniques that may
be applied to AMPs. These molecules represent an exciting resource as anticancer agents with unique
therapeutic advantages that can target challenging mechanisms involving PPIs. Indeed, AMPs are suitable
drug leads for further development of cancer therapeutics, and many studies to this end are underway.
Rapid and selective chemical editing of Ribosomally synthesized and Post‐translationally modified Peptides (RiPPs) via Cu(II)‐catalyzed β‐borylation of dehydroamino acids
