GOF Mutant p53 in Cancers: A Therapeutic Challenge
<i>TP53</i> is mutated in the majority of human cancers. Mutations can lead to loss of p53 expression or expression of mutant versions of the p53 protein. These mutant p53 proteins have oncogenic potential. They can inhibit any remaining WTp53 in a dominant negative manner, or they can a...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/20/5091 |
| _version_ | 1797474518262874112 |
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| author | Lobsang Dolma Patricia A. J. Muller |
| author_facet | Lobsang Dolma Patricia A. J. Muller |
| author_sort | Lobsang Dolma |
| collection | DOAJ |
| description | <i>TP53</i> is mutated in the majority of human cancers. Mutations can lead to loss of p53 expression or expression of mutant versions of the p53 protein. These mutant p53 proteins have oncogenic potential. They can inhibit any remaining WTp53 in a dominant negative manner, or they can acquire new functions that promote tumour growth, invasion, metastasis and chemoresistance. In this review we explore some of the mechanisms that make mutant p53 cells resistant to chemotherapy. As mutant p53 tumours are resistant to many traditional chemotherapies, many have sought to explore new ways of targeting mutant p53 tumours and reinstate chemosensitivity. These approaches include targeting of mutant p53 stability, mutant p53 binding partners and downstream pathways, p53 vaccines, restoration of WTp53 function, and WTp53 gene delivery. The current advances and challenges of these strategies are discussed. |
| first_indexed | 2024-03-09T20:31:16Z |
| format | Article |
| id | doaj.art-987a94e69172420d90e151c0451cee34 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T20:31:16Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-987a94e69172420d90e151c0451cee342023-11-23T23:21:48ZengMDPI AGCancers2072-66942022-10-011420509110.3390/cancers14205091GOF Mutant p53 in Cancers: A Therapeutic ChallengeLobsang Dolma0Patricia A. J. Muller1CRUK Manchester, University of Manchester, Alderley Park, Manchester SK10 4TG, UKDepartment of Biosciences, Durham University, Stockton Road, Durham DH1 3LE, UK<i>TP53</i> is mutated in the majority of human cancers. Mutations can lead to loss of p53 expression or expression of mutant versions of the p53 protein. These mutant p53 proteins have oncogenic potential. They can inhibit any remaining WTp53 in a dominant negative manner, or they can acquire new functions that promote tumour growth, invasion, metastasis and chemoresistance. In this review we explore some of the mechanisms that make mutant p53 cells resistant to chemotherapy. As mutant p53 tumours are resistant to many traditional chemotherapies, many have sought to explore new ways of targeting mutant p53 tumours and reinstate chemosensitivity. These approaches include targeting of mutant p53 stability, mutant p53 binding partners and downstream pathways, p53 vaccines, restoration of WTp53 function, and WTp53 gene delivery. The current advances and challenges of these strategies are discussed.https://www.mdpi.com/2072-6694/14/20/5091mutant p53 chemoresistancetargeted therapygain-of-functionGOF |
| spellingShingle | Lobsang Dolma Patricia A. J. Muller GOF Mutant p53 in Cancers: A Therapeutic Challenge Cancers mutant p53 chemoresistance targeted therapy gain-of-function GOF |
| title | GOF Mutant p53 in Cancers: A Therapeutic Challenge |
| title_full | GOF Mutant p53 in Cancers: A Therapeutic Challenge |
| title_fullStr | GOF Mutant p53 in Cancers: A Therapeutic Challenge |
| title_full_unstemmed | GOF Mutant p53 in Cancers: A Therapeutic Challenge |
| title_short | GOF Mutant p53 in Cancers: A Therapeutic Challenge |
| title_sort | gof mutant p53 in cancers a therapeutic challenge |
| topic | mutant p53 chemoresistance targeted therapy gain-of-function GOF |
| url | https://www.mdpi.com/2072-6694/14/20/5091 |
| work_keys_str_mv | AT lobsangdolma gofmutantp53incancersatherapeuticchallenge AT patriciaajmuller gofmutantp53incancersatherapeuticchallenge |