KLAK peptide in anticancer therapy: Achieving cancer cell apoptosis via mitochondrial membrane disruption using homing domains introduction and other modifications

An amphiphilic α-helical peptide called KLAK (sequence KLAKLAKKLAKLAK) possesses antimicrobial and anticancer activity. KLAK peptide disrupts bacterial membrane as well as eukaryotic mitochondrial membrane, which makes it an interesting tool for killing cancer cells. Nevertheless, the peptide itself suffers from inappropriate distribution in the body, low cell internalization ability causing its insufficient anticancer efficacy and potential toxicity toward the healthy part of the organism. This review focuses on the strategies, which have been widely employed to overcome this obstacle and reach mitochondria destruction and thus enhance anticancer effect in vitro and in vivo in various types of tumors. Various approaches to targeting KLAK towards cancer cells are discussed, such as peptide-based homing domains or amino acid modifications. • KLAK/ d -klak peptide is able to disrupt mitochondrial membrane of cancer cells and thus serves as an interesting tool in anticancer treatment • Use of homing domains overcomes the obstacle of KLAK/ d -klak poor cell entry • Modifications with self-assembly inducing motifs enhance anticancer efficacy of KLAK/ d -klak as well