Abstract
Simple SummaryThe modulation of autophagy represents a potential therapeutic strategy for cancer. More than one hundred clinical trials have been conducted or are ongoing to explore the efficacy of autophagy modulators to reduce the tumor growth and potentiate the anti-cancer effects of conventional therapy. Despite this, the effective role of autophagy during tumor initiation, growth, and metastasis remains not well understood. Depending on the cancer type and stage of cancer, autophagy may have tumor suppressor properties as well as help cancer cells to proliferate and evade cancer therapy. The current review aims to summarize the current knowledge about the autophagy implications in cancer and report the therapeutic opportunities based on the modulation of the autophagy process.The malignant transformation of a cell produces the accumulation of several cellular adaptions. These changes determine variations in biological processes that are necessary for a cancerous cell to survive during stressful conditions. Autophagy is the main nutrient recycling and metabolic adaptor mechanism in eukaryotic cells, represents a continuous source of energy and biomolecules, and is fundamental to preserve the correct cellular homeostasis during unfavorable conditions. In recent decades, several findings demonstrate a close relationship between autophagy, malignant transformation, and cancer progression. The evidence suggests that autophagy in the cancer context has a bipolar role (it may act as a tumor suppressor and as a mechanism of cell survival for established tumors) and demonstrates that the targeting of autophagy may represent novel therapeutic opportunities. Accordingly, the modulation of autophagy has important clinical benefits in patients affected by diverse cancer types. Currently, about 30 clinical trials are actively investigating the efficacy of autophagy modulators to enhance the efficacy of cytotoxic chemotherapy treatments. A deeper understanding of the molecular pathways regulating autophagy in the cancer context will provide new ways to target autophagy for improving the therapeutic benefits. Herein, we describe how autophagy participates during malignant transformation and cancer progression, and we report the ultimate efforts to translate this knowledge into specific therapeutic approaches to treat and cure human cancers.
Highlights
Autophagy is a main catabolic mechanism of the cell and refers to an evolutionary process by which cellular components and damaged organelles are degraded or recycled through lysosomal activity
This review aims to give an intelligible overview of the role of autophagy in cancer formation and progression, describe the complex dual role of autophagy in tumor survival or cell death, summarize the current therapeutic strategies for the treatment of tumors, and, report the most promising clinical trials with autophagy modulators
A wide range of research groups contributed to investigate the important role of the autophagy pathways in cells, from yeast to humans
Summary
Autophagy is a main catabolic mechanism of the cell and refers to an evolutionary process by which cellular components and damaged organelles are degraded or recycled through lysosomal activity. Autophagy occurs as a response to various stress signals and happens at basal levels where it regulates the cellular and tissue development and cell survival/death events [1]. Thanks to these features, today, autophagy is a tightly regulated mechanism involved in diverse pathologies, in particular in cancer, where more than 100 clinical trials associated with autophagy modulation have been conducted or are active. Autophagy is described as a mechanism for the suppression of cancer In this case, autophagy eliminates dangerous cellular elements, preserves the genomics stability, and activates the immunoresponse processes toward malignant transformation. This review aims to give an intelligible overview of the role of autophagy in cancer formation and progression, describe the complex dual role of autophagy in tumor survival or cell death, summarize the current therapeutic strategies for the treatment of tumors, and, report the most promising clinical trials with autophagy modulators
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