Triangular Relationship between p53, Autophagy, and Chemotherapy Resistance
Chemotherapy and radiation often induce a number of cellular responses, such as apoptosis, autophagy, and senescence. One of the major regulators of these processes is p53, an essential tumor suppressor that is often mutated or lost in many cancer types and implicated in early tumorigenesis. Gain of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/8991 |
| _version_ | 1797546618070761472 |
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| author | Jingwen Xu Nipa H. Patel David A. Gewirtz |
| author_facet | Jingwen Xu Nipa H. Patel David A. Gewirtz |
| author_sort | Jingwen Xu |
| collection | DOAJ |
| description | Chemotherapy and radiation often induce a number of cellular responses, such as apoptosis, autophagy, and senescence. One of the major regulators of these processes is p53, an essential tumor suppressor that is often mutated or lost in many cancer types and implicated in early tumorigenesis. Gain of function (GOF) p53 mutations have been implicated in increased susceptibility to drug resistance, by compromising wildtype anti-tumor functions of p53 or modulating key p53 processes that confer chemotherapy resistance, such as autophagy. Autophagy, a cellular survival mechanism, is initially induced in response to chemotherapy and radiotherapy, and its cytoprotective nature became the spearhead of a number of clinical trials aimed to sensitize patients to chemotherapy. However, increased pre-clinical studies have exemplified the multifunctional role of autophagy. Additionally, compartmental localization of p53 can modulate induction or inhibition of autophagy and may play a role in autophagic function. The duality in p53 function and its effects on autophagic function are generally not considered in clinical trial design or clinical therapeutics; however, ample pre-clinical studies suggest they play a role in tumor responses to therapy and drug resistance. Further inquiry into the interconnection between autophagy and p53, and its effects on chemotherapeutic responses may provide beneficial insights on multidrug resistance and novel treatment regimens for chemosensitization. |
| first_indexed | 2024-03-10T14:32:15Z |
| format | Article |
| id | doaj.art-9fc74a24d0404d04aab9fa5aa0641b49 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:32:15Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9fc74a24d0404d04aab9fa5aa0641b492023-11-20T22:29:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012123899110.3390/ijms21238991Triangular Relationship between p53, Autophagy, and Chemotherapy ResistanceJingwen Xu0Nipa H. Patel1David A. Gewirtz2School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaMassey Cancer Center, Goodwin Research Laboratories, Virginia Commonwealth University, Richmond, VA 23298, USAMassey Cancer Center, Goodwin Research Laboratories, Virginia Commonwealth University, Richmond, VA 23298, USAChemotherapy and radiation often induce a number of cellular responses, such as apoptosis, autophagy, and senescence. One of the major regulators of these processes is p53, an essential tumor suppressor that is often mutated or lost in many cancer types and implicated in early tumorigenesis. Gain of function (GOF) p53 mutations have been implicated in increased susceptibility to drug resistance, by compromising wildtype anti-tumor functions of p53 or modulating key p53 processes that confer chemotherapy resistance, such as autophagy. Autophagy, a cellular survival mechanism, is initially induced in response to chemotherapy and radiotherapy, and its cytoprotective nature became the spearhead of a number of clinical trials aimed to sensitize patients to chemotherapy. However, increased pre-clinical studies have exemplified the multifunctional role of autophagy. Additionally, compartmental localization of p53 can modulate induction or inhibition of autophagy and may play a role in autophagic function. The duality in p53 function and its effects on autophagic function are generally not considered in clinical trial design or clinical therapeutics; however, ample pre-clinical studies suggest they play a role in tumor responses to therapy and drug resistance. Further inquiry into the interconnection between autophagy and p53, and its effects on chemotherapeutic responses may provide beneficial insights on multidrug resistance and novel treatment regimens for chemosensitization.https://www.mdpi.com/1422-0067/21/23/8991p53autophagychemoresistance |
| spellingShingle | Jingwen Xu Nipa H. Patel David A. Gewirtz Triangular Relationship between p53, Autophagy, and Chemotherapy Resistance International Journal of Molecular Sciences p53 autophagy chemoresistance |
| title | Triangular Relationship between p53, Autophagy, and Chemotherapy Resistance |
| title_full | Triangular Relationship between p53, Autophagy, and Chemotherapy Resistance |
| title_fullStr | Triangular Relationship between p53, Autophagy, and Chemotherapy Resistance |
| title_full_unstemmed | Triangular Relationship between p53, Autophagy, and Chemotherapy Resistance |
| title_short | Triangular Relationship between p53, Autophagy, and Chemotherapy Resistance |
| title_sort | triangular relationship between p53 autophagy and chemotherapy resistance |
| topic | p53 autophagy chemoresistance |
| url | https://www.mdpi.com/1422-0067/21/23/8991 |
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