Cancer formation is a highly regulated and complex process, largely dependent on its microenvironment. This complexity highlights the need for developing novel target-based therapies depending on cancer phenotype and genotype. Autophagy, a catabolic process, removes damaged and defective cellular materials through lysosomes. It is activated in response to stress conditions such as nutrient deprivation, hypoxia, and oxidative stress. Oxidative stress is induced by excess reactive oxygen species (ROS) that are multifaceted molecules that drive several pathophysiological conditions, including cancer. Moreover, autophagy also plays a dual role, initially inhibiting tumor formation but promoting tumor progression during advanced stages. Mounting evidence has suggested an intricate crosstalk between autophagy and ROS where they can either suppress cancer formation or promote disease etiology. This review highlights the regulatory roles of autophagy and ROS from tumor induction to metastasis. We also discuss the therapeutic strategies that have been devised so far to combat cancer. Based on the review, we finally present some gap areas that could be targeted and may provide a basis for cancer suppression.
The autophagy mechanism recycles the damaged and long-standing macromolecular substrates and thus maintains cellular homeostatic and proteostatic conditions. Autophagy can be an unavoidable target in cancer therapy because its deregulation leads to cancer formation and progression. Cancer can be controlled by regulating autophagy at different genetic, epigenetic, and post-translational levels. Epigenetics refers to the heritable phenotypic changes that affect gene activity without changing the sequence. Modern biology employs epigenetic alterations as molecular tools to detect and treat a wide range of disorders, including cancer. However, modulating autophagy at the epigenetic level may inhibit cancer growth and progression. Epigenetics-targeting drugs involved in preclinical and clinical trials may trigger antitumor immunity. Here, we have reviewed some experimental evidence in which epigenetics have been used to control deregulated autophagy in cancerous diseases. Furthermore, we also reviewed some current clinical trials of epigenetic therapy against cancer. We hope that this information can be utilized in the near future to treat and overcome cancer.
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