Article ; Online: Autophagy and PTEN in DNA damage-induced senescence.
2021 Volume 150, Page(s) 249–284
Abstract: The use of DNA-damaging agents such as radiotherapy and chemotherapy has been a mainstay treatment protocol for many cancers, including lung and prostate. Recently, FDA approval of inhibitors of DNA repair, and targeting innate immunity to enhance the ... ...
| Abstract | The use of DNA-damaging agents such as radiotherapy and chemotherapy has been a mainstay treatment protocol for many cancers, including lung and prostate. Recently, FDA approval of inhibitors of DNA repair, and targeting innate immunity to enhance the efficacy of DNA-damaging agents have gained much attention. Yet, inherent or acquired resistance against DNA-damaging therapies persists as a fundamental drawback. While cancer eradication by causing cancer cell death through induction of apoptosis is the ultimate goal of anti-cancer treatments, autophagy and senescence are two major cellular responses induced by clinically tolerable doses of DNA-damaging therapies. Unlike apoptosis, autophagy and senescence can act as both pro-tumorigenic as well as tumor suppressive mechanisms. DNA damage-induced senescence is associated with a pro-inflammatory secretory phenotype, which contributes to reshaping the tumor- immune microenvironment. Moreover, PTEN (phosphatase and tensin homolog) is a tumor supressor deleted in many tumors, and has been implicated in both senescence and autophagy. This review presents an overview of the literature on the regulation and consequences of DNA damage- induced senescence in cancer cells, with a specific focus on autophagy and PTEN. Both autophagy and senescence occur concurrently in the same cells in response to DNA damaging agents. However, a deterministic relationship between these fundamental processes has been controversial. We present experimental evidence obtained with tumor cells, with a prime focus on two models of cancer, prostate and lung. A better understanding of mechanisms associated with DNA damage-induced cellular senescence is central to fully exploit the potential of DNA-damaging agents against cancer. |
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| MeSH term(s) | Animals ; Apoptosis/genetics ; Autophagy/physiology ; Cellular Senescence/genetics ; DNA Damage/genetics ; DNA Damage/physiology ; Female ; Humans ; Male ; PTEN Phosphohydrolase/genetics ; PTEN Phosphohydrolase/physiology ; Signal Transduction/genetics ; Tumor Microenvironment |
| Chemical Substances | PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67) |
| Language | English |
| Publishing date | 2021-03-03 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review |
| ZDB-ID | 127-2 |
| ISSN | 2162-5557 ; 0065-230X |
| ISSN (online) | 2162-5557 |
| ISSN | 0065-230X |
| DOI | 10.1016/bs.acr.2021.01.006 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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