The Role of Autophagy in Cancer

Autophagy is a conserved homeostatic pathway involved in degradation and recycling of cellular components. It is important in adapting to stress conditions like nutrient deprivation, organelle damage and accumulation of intracellular proteins. The process starts with the formation of special compartments that engulf the cargo to be degraded and deliver it to lysosomes for degradation. This turnover plays a crucial role in cancer biology, where tumor progression and suppression are both modulated by autophagy. In early-stage tumorigenesis, autophagy inhibits initiation by preserving genomic stability, reducing oxidative stress, and preventing inflammation. Conversely, at advanced tumor stages, autophagy maintains metabolism to support cancer cell survival. Its complex role in cancer metabolism, involving glucose, amino acids, and lipids, underlines its importance in tumors. Autophagy also displays immunomodulatory roles in tumor dormancy, metastasis, and immune evasion, linking metabolic pathways to immune response. All these factors make autophagy manipulation a better stance to target autophagy against cancer therapeutically. Drugs such as hydroxychloroquine, are autophagy modulators that are being clinically evaluated in combination therapy against cancer to improve patient outcomes. However, the bidirectional role of autophagy in cancer makes it difficult to understand whether to enhance autophagy inside cancerous cells or to target the same. Understanding context-dependent autophagy manipulation in cancers could provide better solutions to optimize therapeutic strategies in cancer treatments. In this chapter, we present the complex dynamics of autophagy in cancer cells. Figure 13.1 describes the process of autophagy in cells.