Autophagy modulation as a potential _targeted cancer therapy: From drug repurposing to new drug development

doi:10.1002/kjm2.12361

Review

. 2021 Mar;37(3):166-171.

doi: 10.1002/kjm2.12361. Epub 2021 Jan 26.

Autophagy modulation as a potential _targeted cancer therapy: From drug repurposing to new drug development

Chia-Jung Lin¹, Yuan-Ni Tsao¹, Chih-Wen Shu^{1

2

3}

Affiliations

¹ Institute of Biopharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
² Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
³ Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.

PMID: 33496377
DOI: 10.1002/kjm2.12361

Free article

Review

Autophagy modulation as a potential _targeted cancer therapy: From drug repurposing to new drug development

Chia-Jung Lin et al. Kaohsiung J Med Sci. 2021 Mar.

Free article

. 2021 Mar;37(3):166-171.

doi: 10.1002/kjm2.12361. Epub 2021 Jan 26.

Authors

Chia-Jung Lin¹, Yuan-Ni Tsao¹, Chih-Wen Shu^{1

2

3}

Affiliations

¹ Institute of Biopharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
² Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
³ Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.

PMID: 33496377
DOI: 10.1002/kjm2.12361

Abstract

Autophagy is an evolutionarily conserved signaling pathway to deliver dysfunctional proteins or organelles into lysosomes for degradation and recycling, which is an important pathway for normal homeostasis. Autophagy dysfunction can lead to various diseases, particularly cancer. Autophagy not only plays a role in tumor suppression, but it also serves as a tumor promoter in cancer malignancy. In this review, we summarize the involvement of autophagy-related (ATG) proteins in autophagy signaling and the role of autophagy in cancer progression. The effectiveness of US Food and Drug Administration-approved drugs in regulating autophagic flux and suppressing cancer cells is also discussed. Moreover, since clinically available drugs do not specifically _target ATG proteins, there is little doubt that their cancer suppression function is autophagy dependent. Therefore, this review also discusses several inhibitors against ATG proteins, such as ULK1/2, ATG4, and VPS34 to suppress cancer cells. Autophagy modulators can be either used alone or combined with chemotherapy or radiation therapy to enhance the efficacy of current treatments for certain types of cancer. This review summarizes current autophagy modulation used as a potential strategy for _targeted cancer therapy.

Keywords: ATG protein; anti-cancer drug; autophagy; inducer; inhibitor.

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References

REFERENCES

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[1] Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal. 2014;20(3):460-473.

[2] Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal. 2014;20(3):460-473.

[3] Ghosh R, Pattison JS. Macroautophagy and chaperone-mediated autophagy in heart failure: the known and the unknown. Oxid Med Cell Longev. 2018;1-22.

[4] Ghosh R, Pattison JS. Macroautophagy and chaperone-mediated autophagy in heart failure: the known and the unknown. Oxid Med Cell Longev. 2018;1-22.

[5] Liu PF, Farooqi AA, Peng SY, Yu TJ, Dahms HU, Lee CH, et al. Regulatory effects of noncoding RNAs on the interplay of oxidative stress and autophagy in cancer malignancy and therapy. Semin Cancer Biol. 2020;S1044-579X(20):30214-30215.

[6] Liu PF, Farooqi AA, Peng SY, Yu TJ, Dahms HU, Lee CH, et al. Regulatory effects of noncoding RNAs on the interplay of oxidative stress and autophagy in cancer malignancy and therapy. Semin Cancer Biol. 2020;S1044-579X(20):30214-30215.

[7] Zhou C, Ma K, Gao R, Mu C, Chen L, Liu Q, et al. Regulation of mATG9 trafficking by Src- and ULK1-mediated phosphorylation in basal and starvation-induced autophagy. Cell Res. 2017;27(2):184-201.

[8] Zhou C, Ma K, Gao R, Mu C, Chen L, Liu Q, et al. Regulation of mATG9 trafficking by Src- and ULK1-mediated phosphorylation in basal and starvation-induced autophagy. Cell Res. 2017;27(2):184-201.

[9] Otomo C, Metlagel Z, Takaesu G, Otomo T. Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy. Nat Struct Mol Biol. 2013;20(1):59-66.

[10] Otomo C, Metlagel Z, Takaesu G, Otomo T. Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy. Nat Struct Mol Biol. 2013;20(1):59-66.

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Autophagy modulation as a potential _targeted cancer therapy: From drug repurposing to new drug development

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Autophagy modulation as a potential _targeted cancer therapy: From drug repurposing to new drug development

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