Antimicrobial Peptides as Anticancer Peptides: The Strategies to Overcome Multidrug Resistance in Cancer

Boonpipob  Klomklao; Michael W  Chan; Tistaya  Semangoen; Sirin Saranyutanon

Authors

Boonpipob Klomklao Faculty of Allied Health Sciences, Burapha University, Chonburi, Thailand
Michael W Chan Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi, Japan
Tistaya Semangoen Faculty of Allied Health Sciences, Burapha University, Chonburi, Thailand
Sirin Saranyutanon Faculty of Allied Health Sciences, Burapha University, Chonburi, Thailand

Keywords:

Antimicrobial peptides, Anticancer peptides, Multidrug resistance, Cancer chemotherapeutics, Peptide therapeutics

Abstract

Cancer remains a leading cause of global mortality. Although chemotherapy is a primary treatment, its therapeutic efficacy is frequently compromised by multidrug resistance (MDR). Multiple factors contribute to this resistance, including ABC transporter-driven drug efflux, evasion of cell death, altered autophagy, tumor microenvironment changes, and persistent cancer stem cells. While MDR has been widely studied, we still lack a clear, comprehensive picture of how the structure of antimicrobial peptides (AMPs) helps them act as anticancer agents and break through this resistance. In this review, we cover the sources, structural traits, structure-activity links, and cancer-targeting abilities of AMPs. This review highlights major MDR mechanisms and explores how AMPs defeat treatment limits through varied actions, from membrane disruption and ROS production to immune modulation, mitochondrial damage, and ABC transporter blockade. Additionally, it also examines chemical modifications, sequence engineering, and nanocarrier delivery systems designed to enhance peptide stability, targeting, and therapeutic efficacy.

Overall, AMPs show strong potential as multi-target anticancer agents that can reduce both drug resistance and side effects. Still, issues like rapid breakdown in the body, low bioavailability, high production costs, and delivery obstacles limit their clinical use. Combining promising sequence engineering with innovative delivery systems will be key to overcoming these barriers and unlocking their therapeutic value.

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