Antimicrobial peptides (AMPs), also called host defense peptides (HDPs), are identified in almost any form of life, which play an important role in innate immune systems. They have a broad spectrum of antifungal, antiviral, antibacterial, and anticancer activities. Lung cancer remains the leading cause of global cancer-related death. Unfortunately, lung cancer chemotherapy is accompanied by serious side effects, nonspecific toxicity, and multidrug resistance. Hence, to overcome these drawbacks, anticancer peptides (ACPs) derived from AMPs may represent a potential promising synergistic treatment strategy for lung cancer.

In this review, the authors provide the recent advancements in the use of AMPs for the treatment of lung cancer. Furthermore, the anti-lung cancer modes of action of these peptides have been fully reviewed. Importantly, various strategies for increasing the efficiency and safety of AMPs have been discussed.

The combination of AMPs and other cancer treatment approaches such as chemotherapy, nanoparticle-based delivery systems, and photodynamic therapy can be used as a promising revolutionary strategy for the treatment of lung cancer. The most significant limitations of this strategy that need to be focused on are low efficiency and off-target events.