p53-Dependent Cytoprotective Mechanisms behind Resistance to Chemo-Radiotherapeutic Agents Used in Cancer Treatment
Resistance to chemoradiotherapy is the main cause of cancer treatment failure. Cancer cells, especially cancer stem cells, utilize innate cytoprotective mechanisms to protect themselves from the adverse effects of chemoradiotherapy. Here, we describe a few such mechanisms: DNA damage response (DDR),...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/13/3399 |
| _version_ | 1797591991336304640 |
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| author | Jayaraman Krishnaraj Tatsuki Yamamoto Rieko Ohki |
| author_facet | Jayaraman Krishnaraj Tatsuki Yamamoto Rieko Ohki |
| author_sort | Jayaraman Krishnaraj |
| collection | DOAJ |
| description | Resistance to chemoradiotherapy is the main cause of cancer treatment failure. Cancer cells, especially cancer stem cells, utilize innate cytoprotective mechanisms to protect themselves from the adverse effects of chemoradiotherapy. Here, we describe a few such mechanisms: DNA damage response (DDR), immediate early response gene 5 (IER5)/heat-shock factor 1 (HSF1) pathway, and p21/nuclear factor erythroid 2–related factor 2 (NRF2) pathway, which are regulated by the tumour suppressor p53. Upon DNA damage caused during chemoradiotherapy, p53 is recruited to the sites of DNA damage and activates various DNA repair enzymes including GADD45A, p53R2, DDB2 to repair damaged-DNA in cancer cells. In addition, the p53-IER5-HSF1 pathway protects cancer cells from proteomic stress and maintains cellular proteostasis. Further, the p53-p21-NRF2 pathway induces production of antioxidants and multidrug resistance-associated proteins to protect cancer cells from therapy-induced oxidative stress and to promote effusion of drugs from the cells. This review summarises possible roles of these p53-regulated cytoprotective mechanisms in the resistance to chemoradiotherapy. |
| first_indexed | 2024-03-11T01:45:27Z |
| format | Article |
| id | doaj.art-c61f5501180e420f918d49c00f334b84 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T01:45:27Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c61f5501180e420f918d49c00f334b842023-11-18T16:16:27ZengMDPI AGCancers2072-66942023-06-011513339910.3390/cancers15133399p53-Dependent Cytoprotective Mechanisms behind Resistance to Chemo-Radiotherapeutic Agents Used in Cancer TreatmentJayaraman Krishnaraj0Tatsuki Yamamoto1Rieko Ohki2Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, JapanLaboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, JapanLaboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, JapanResistance to chemoradiotherapy is the main cause of cancer treatment failure. Cancer cells, especially cancer stem cells, utilize innate cytoprotective mechanisms to protect themselves from the adverse effects of chemoradiotherapy. Here, we describe a few such mechanisms: DNA damage response (DDR), immediate early response gene 5 (IER5)/heat-shock factor 1 (HSF1) pathway, and p21/nuclear factor erythroid 2–related factor 2 (NRF2) pathway, which are regulated by the tumour suppressor p53. Upon DNA damage caused during chemoradiotherapy, p53 is recruited to the sites of DNA damage and activates various DNA repair enzymes including GADD45A, p53R2, DDB2 to repair damaged-DNA in cancer cells. In addition, the p53-IER5-HSF1 pathway protects cancer cells from proteomic stress and maintains cellular proteostasis. Further, the p53-p21-NRF2 pathway induces production of antioxidants and multidrug resistance-associated proteins to protect cancer cells from therapy-induced oxidative stress and to promote effusion of drugs from the cells. This review summarises possible roles of these p53-regulated cytoprotective mechanisms in the resistance to chemoradiotherapy.https://www.mdpi.com/2072-6694/15/13/3399drug-resistanceDNA damage responsep53IER5NRF2 |
| spellingShingle | Jayaraman Krishnaraj Tatsuki Yamamoto Rieko Ohki p53-Dependent Cytoprotective Mechanisms behind Resistance to Chemo-Radiotherapeutic Agents Used in Cancer Treatment Cancers drug-resistance DNA damage response p53 IER5 NRF2 |
| title | p53-Dependent Cytoprotective Mechanisms behind Resistance to Chemo-Radiotherapeutic Agents Used in Cancer Treatment |
| title_full | p53-Dependent Cytoprotective Mechanisms behind Resistance to Chemo-Radiotherapeutic Agents Used in Cancer Treatment |
| title_fullStr | p53-Dependent Cytoprotective Mechanisms behind Resistance to Chemo-Radiotherapeutic Agents Used in Cancer Treatment |
| title_full_unstemmed | p53-Dependent Cytoprotective Mechanisms behind Resistance to Chemo-Radiotherapeutic Agents Used in Cancer Treatment |
| title_short | p53-Dependent Cytoprotective Mechanisms behind Resistance to Chemo-Radiotherapeutic Agents Used in Cancer Treatment |
| title_sort | p53 dependent cytoprotective mechanisms behind resistance to chemo radiotherapeutic agents used in cancer treatment |
| topic | drug-resistance DNA damage response p53 IER5 NRF2 |
| url | https://www.mdpi.com/2072-6694/15/13/3399 |
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