Cancer, as a remaining challenging medical problem, affects millions of people around the world. Cancer cell resistance is one of the main drawbacks in the complete prosperity of even more sophisticated therapies. Pore-forming peptides (PFPs), a group of natural defense system’s proteins used by nearly whole living organisms as antibacterial and antifungal agents, could also be regarded as novel tumoricidal peptides. PFPs approach entails the use of soluble peptides by assembling on mainly target cell membrane and forming potential death-causing pores. Physical damage induction by natural PFPs or their synthetic derivatives could conquer the resistance mechanisms of tumor cells. Given that peptide drugs involve a significant proportion of the pharmaceutical market primarily because of easy synthesis and safety, evaluation of this nature provided model system as a group of anticancer peptides seems a valuable approach. Here, the mode of action of PFPs and their anticancer mechanism are highlighted which is followed by addressing the anticancer studies using PFPs from various sources along with various applied strategies to obtain selective action of PFPs against cancer cells. Challenges and future perspectives of these promising bioactive molecules in cancer treatment are also provided.
