Exploring the Functional Significance of Lysosomes in Cancer Drug Resistance

Abstract

Chemotherapy stands as a primary therapeutic approach for tackling a spectrum of malignancies. Nonetheless, the emergence of resistance to chemotherapeutic agents poses a significant hurdle in achieving curative cancer treatments. Lysosomes, recognized as acidic cellular organelles predominantly engaged in intracellular digestion, have garnered increasing attention due to their implications in cancer biology. Notably, their relevance to cancer manifests in several ways: Firstly, the extracellular release of lysosomal enzymes actively promotes tumorigenesis. Secondly, the leakage of lysosomal hydrolases into the cytosol induces apoptosis. Lastly, weak chemotherapeutic bases, upon traversing the lysosomal membrane, become sequestered within lysosomes while adopting a cationic state. This sequestration of drugs within lysosomes diminishes their cytotoxic potential, restricts their availability at target sites, and contributes significantly to the development of drug resistance in cancer. This review comprehensively explores diverse mechanisms underpinning lysosomal drug sequestration and delves into their repercussions on the phenomenon of multidrug resistance in cancer. Furthermore, we delve into strategies aimed at surmounting drug resistance by leveraging lysosomes as subcellular targets, with the aim of reversing drug sequestration and thwarting drug resistance in the context of cancer therapy