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Normal cells depend on autophagy to maintain cellular homeostasis by recycling damaged organelles and misfolded proteins and degrading toxic agents. Similar to apoptosis, targeting autophagy has been under attention in cancer therapy. However, autophagy has both pro-survival and pro-death functions in tumors, and its targeting requires further elucidation. The current review focuses on using nanoparticles for targeting autophagy in cancer treatment. Nanocarriers can deliver autophagy regulators along with chemotherapeutic agents leading to intracellular accumulation in cancer cells and synergistic cancer therapy. Furthermore, genetic tools such as siRNA and shRNA can be used for targeting molecular components that regulate autophagy, such as the ATG12-ATG5-ATG16L1 complex. A number of nanostructures, such as gold and zinc oxide nanoparticles, can be used to enhance oxidative stress-mediated apoptosis and autophagy, reducing cancer progression. Further, using nanoparticles to modulate autophagy potentiates the anti-tumor effects of cisplatin and gefitinib during chemotherapy. Polymeric nanoparticles, lipid-based nanostructures and carbon-based nanomaterials are among other nanoparticles capable of regulating autophagy in cancer cells. Of note, various regulatory components of autophagy such as ATGs, Beclin-1 and LC3-II can be affected by nanomaterials. Based on the role of nanomaterial-induced autophagy as pro-survival or pro-death, further targeting can potentiate the fight against cancer cells., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Lung cancer (LC) is a leading cause of death worldwide with high mortality and morbidity. A wide variety of risk factors are considered for LC development such as smoking, air pollution and family history. It appears that genetic and epigenetic factors are also potential players in LC development and progression. AMP-activated protein kinase (AMPK) is a signaling pathway with vital function in inducing energy balance and homeostasis. An increase in AMP:ATP and ADP:ATP ratio leads to activation of AMPK signaling by upstream mediators such as LKB1 and CamKK. Dysregulation of AMPK signaling is a common finding in different cancers, particularly LC. AMPK activation can significantly enhance LC metastasis via EMT induction. Upstream mediators such as PLAG1, IMPAD1, and TUFM can regulate AMPK-mediated metastasis. AMPK activation can promote proliferation and survival of LC cells via glycolysis induction. In suppressing LC progression, anti-tumor compounds including metformin, ginsenosides, casticin and duloxetine dually induce/inhibit AMPK signaling. This is due to double-edged sword role of AMPK signaling in LC cells. Furthermore, AMPK signaling can regulate response of LC cells to chemotherapy and radiotherapy that are discussed in the current review., (Copyright © 2021 Elsevier Inc. All rights reserved.)