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Review
. 2021 Aug 17;11(8):839.
doi: 10.3390/life11080839.

Autophagy Modulators in Cancer: Focus on Cancer Treatment

Hye Jin Nam  1
Affiliations
Review

Autophagy Modulators in Cancer: Focus on Cancer Treatment

Hye Jin Nam. Life (Basel). .

Abstract

Uncontrolled autophagy has been associated with the development and progression of various cancers that are resistant to cancer therapy. Therefore, many efforts to modulate uncontrolled autophagy as a cancer treatment have been attempted, from basic science to clinical trials. However, it remains difficult to equally apply autophagy modulators to cancer therapy because autophagy is a double-edged sword in cancer: it can be tumor-suppressive or tumor-protective. Therefore, the precise mechanisms of autophagy modulators and their varied responsiveness to each cancer type should be addressed in detail. This study will describe the precise mechanisms of developing various autophagy modulators, their current therapeutic applications and future perspectives.

Keywords: autophagy; autophagy enhancer; autophagy inhibitor; cancer treatment.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Schematic diagram of autophagic progression. There are three types of autophagy in mammalian cells: macroautophagy, microautophagy and chaperone-mediated autophagy. When macroautophagy is induced, cytoplasmic materials are engulfed by double membranes (phagophore), closed (autophagosome), fused with the lysosome (autolysosome) and degraded. The KFERQ motif is recognized by Hsc70 and binds with LAMP2A in CMA. LAMP2A mediates the translocation of the substrate into lysosomes. Microautophagy directly uptakes the cytoplasmic cargo.
Figure 2
Figure 2
Signaling cascades and modulators that regulate autophagy initiation.The energy sensors, mTOR and AMP-activated kinase (AMPK), are the primary regulators of autophagy. AMPK activation or mTOR inhibition induces autophagy. Activated AMPK phosphorylates ULK1/2, and autophagy is then initiated. Various autophagy modulators and their targets are shown in the figure.
Figure 3
Figure 3
Lysosomal inhibitors. Autophagy is inhibited by lysosomal inhibitors. Lysosomal activity is inhibited by increasing intralysosomal pH or inhibiting v-ATPase.
Figure 4
Figure 4
Histone H3 modifications associated with autophagy regulation.Histone H3 tail is methylated by G9a, EZH2 or CARM1. The epigenetic modulators can induce autophagy (inhibitor of H3K27 me) or block induced autophagy (inhibitor of H3R17 me).
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