Targeting Lysosomes for Enhanced Anti-Cancer Therapeutics and Immune Response

Cancer is a leading cause of death in Western countries. Apart from surgical resection, the primary treatment modalities chemotherapy and radiotherapy inflict serious side effects, and significantly remodel both tumor metabolism and the tumor microenvironment. This consequently compromises treatment efficacy, resulting in multiple drug resistance, immune evasion and cancer progression. Lysosomes are unique acidic intracellular organelles crucial for maintaining cellular health and homeostasis via degradation of cellular waste. Lysosomes are also required for autophagy, a stress-induced catabolic pathway that is important for cell survival. Autophagy is typically enhanced in tumor cells, as it can confer cyto-protection against the deleterious cytotoxic effects of chemotherapy, and suppress anti-cancer immune response. Owing to their acidic nature and their role in endocytosis, lysosomes can be readily targeted and manipulated, thus attenuating the autophagic flux and improving cancer treatment outcome. Herein we focused on various classic and innovative lysosome modulators, their impact on autophagy, the enhancement of immune response, and consequent inhibition of tumor growth and metastasis. We discuss modalities to minimize adverse effects in cancer patients by either utilizing harmless compounds, achieving synergistic activity with combination therapies, or specifically targeting the tumor by using advanced nanoparticle technologies.