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Autophagy is a highly conserved catabolic process that enables cells to degrade and recycle cytoplasmic components—including damaged organelles and misfolded proteins—via the formation of double-membrane vesicles called autophagosomes that fuse with lysosomes for content breakdown. In tumor cells, autophagy plays complex roles. It can act as a tumor suppressor by maintaining cellular quality control and preventing the accumulation of oncogenic damage during early stages. However, once tumors are established, enhanced autophagic activity often supports cancer cell survival under stressful conditions such as hypoxia, nutrient deprivation, metabolic stress, chemotherapy exposure, or immune attack. This duality means that both activation and inhibition of autophagy have been explored therapeutically—activation may prevent initiation/progression while inhibition may sensitize established cancers to treatment. Autophagic flux is regulated by numerous genes known as ATGs; disruptions or mutations in these genes are implicated across various diseases including cancer. In the tumor microenvironment specifically, modulation of autophagy affects immune responses—sometimes promoting antitumor immunity via improved antigen presentation but also potentially enabling immune evasion through increased expression of inhibitory molecules like PD-L1/PD-L2 on tumor cells. Pharmacological agents such as chloroquine/hydroxychloroquine inhibit late-stage autophagic flux by blocking lysosomal acidification; these drugs are being investigated clinically for their ability to sensitize tumors to chemotherapy or immunotherapy. Biomarkers like LC3 puncta formation serve as indicators for monitoring therapeutic efficacy. Importantly—and unlike classical molecular targets such as receptors or enzymes—"autophagy in tumor cells" refers not to a single protein but rather an orchestrated network/process involving many molecular players.[1][2][3]
Inhibition of lysosomal acidification to block autophagosome degradation (e.g., chloroquine/hydroxychloroquine)
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