Abstract
Cancer continues to be a leading source of morbidity and mortality worldwide in spite of progress in oncolytic therapies. In addition, the incidence of cancers affecting the breast, kidney, prostate and skin among others continue to rise. Chemotherapeutic drugs are widely used in cancer treatment but have the serious drawback of nonspecific toxicity because these agents target any rapidly dividing cell without discriminating between healthy and malignant cells. In addition, many neoplasms eventually become resistant to conventional chemotherapy due to selection for multidrug-resistant variants. The limitations associated with existing chemotherapeutic drugs have stimulated the search for new oncolytic therapies. Host defense peptides (HDPs) may represent a novel family of oncolytic agents that can avoid the shortcomings of conventional chemotherapy because they exhibit selective cytotoxicity against a broad spectrum of malignant human cells, including multi-drug-resistant neoplastic cells. Oncolytic activity by HDPs is usually via necrosis due to cell membrane lysis, but some HDPs can trigger apoptosis in cancer cells via mitochondrial membrane disruption. In addition, certain HDPs are anti-angiogenic which may inhibit cancer progression. This paper reviews oncolytic HDP studies in order to address the suitability of selected HDPs as oncolytic therapies.
Highlights
The human immune system mainly recognizes and eliminates malignant cells via receptor-mediated mechanisms
It has been demonstrated that Host defense peptides (HDPs) induce cell death of transformed cells, but are much less cytotoxic to non-transformed cells [7,9,28,29,30,31,32,33,34,35,36,37,38]. These results suggest that HDPs may have future value as oncolytic drugs either alone or in combination with conventional therapies
The potential of magainin II as an oncolytic drug is enhanced by the fact that its unique mechanism of cell killing is unaffected by the multidrug resistance (MDR) phenotype in human melanoma and small-cell lung carcinoma [35,76]
Summary
The human immune system mainly recognizes and eliminates malignant cells via receptor-mediated mechanisms. The immune response can play a significant role in controlling malignant growth under natural conditions or in response to therapeutic manipulation, but malignant cells may evade immune surveillance [1,2] Conventional cytotoxic therapies, such as radiation and chemotherapy, are the methods of choice for cancer management. Numerous chemotherapeutic drugs have been developed to treat cancers, including DNA-alkylating agents, antimetabolites, and hormone agonists/antagonists These drugs have been successfully used for the treatment of metastatic cancers, severe side-effects and dose limitations are prevalent. A promising family includes host defence peptides (HDPs) that recently have received attention as alternative chemotherapeutic agents that overcome the limits of current drugs These peptides have several advantages over currently used oncolytic therapeutics, such as selective cytotoxicity for cancer cells, ability to bypass the multidrug-resistance mechanism, and additive effects in combination therapy [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
