The roles, controversies, and combination therapies of autophagy in lung cancer

Abstract

Lung cancer is one of the leading causes of death among men and women worldwide. The disease initially has a silent phenotype, which leads to the progression of the disease and ultimately the lack of proper response to routine treatments. Autophagy, known as an intracellular “recycle bin” for the degradation of defective proteins and molecules, is one of the mechanisms that has been considered in the context of cancer in recent years. This study aims to provide a comprehensive review of published articles on autophagy in the context of lung cancer to have a complete view of the role of autophagy in lung cancer and its possible treatments. PubMed, Scopus, and Google Scholar were searched until June 15 to find related articles. No specific search filters or restrictions were applied. The results were entered into reference management software for aggregation and management. The full text of all articles was screened and studied. In conclusion, studies on the exact function of autophagy in lung cancer are contradictory, but what can be concluded from a review of literature on lung cancer is that targeting autophagy combined with traditional routine therapies such as chemotherapy, especially in advanced stages of lung cancer, can be an effective anticancer approach.

DSTYK inhibition increases the sensitivity of lung cancer cells to T cell–mediated cytotoxicity

“…In recent years, modulating autophagy has been proposed as a promising treatment for lung cancer, as it plays a central role in tumorigenesis and tumor progression ( Nam, 2021 ; Wang et al, 2022 ). Autophagy seems to be a double-edge sword, as it can play both cytoprotective and cytotoxic roles in cells, in a context-specific way ( Colhado Rodrigues et al, 2020 ).…”

“…In the early stages of cancer development, autophagy is believed to protect the cells against cancer initiation. Once a tumor is established, the neighboring microenvironment is often hypoxic and nutrient-deprived, and autophagy fuels and supports cancer cells growth, switching into a tumor promoter role ( Wang et al, 2022 ). Autophagy also promotes epithelial–mesenchymal transition, migration, and invasion of tumoral cells ( Li et al, 2013 ; Zhu et al, 2014 ; Luo et al, 2018 ).…”

Global research and emerging trends in autophagy in lung cancer: a bibliometric and visualized study from 2013 to 2022

“…Autophagy is an intracellular degradation and recycling mechanism that helps cells cope with various environmental stresses and, to some extent, participates in the regulation of cell death. During chemotherapy and radiotherapy, lung cancer cells often employ autophagy as a mechanism to mitigate intracellular damage and stress, thereby enhancing cell survival and evading therapeutic effects ( Guo et al, 2022 ; Wang et al, 2022 ). Research has demonstrated that lung cancer cells exhibit heightened autophagic activity after prolonged chemotherapy or targeted treatment, resulting in the degradation of drug target proteins and repair-capable proteins.…”

Deciphering the Effects and Mechanisms of Yi-Fei-San-Jie-pill on Non-Small Cell Lung Cancer With Integrating Network Target Analysis and Experimental Validation

“…Nonetheless, mitochondria were corroborated to promote aerobic oxidation for lung cancer survival and metastasis ( Li F. et al, 2020 ; Sorrenti et al, 2021 ). The latest review also shows that the combination of traditional therapies and autophagy inhibitors including 3-MA can improve the efficacy of lung cancer ( Wang Z. et al, 2021 ), and even intervention in specific autophagy genes can improve the response rate of immunotherapy ( Lawson et al, 2020 ). We have revealed that YFSJ-treated patients express higher microRNA-182 than those in the control group, and microRNA-182 was predicted and verified to target Atg7 (data not shown).…”