Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated Cancers
Mutations in the p53 gene are frequently observed in various cancers, prompting the initiation of efforts to restore p53 function as a therapeutic approach several decades ago. Nevertheless, only a limited number of drug development initiatives have progressed to late-stage clinical trials, and to d...
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MDPI AG
2025-05-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/15/6/763 |
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| author | Na Zhang Zhiyuan Jing Jie Song Qiyue Liang Yuxue Xu Zhaowei Xu Longping Wen Pengfei Wei |
| author_facet | Na Zhang Zhiyuan Jing Jie Song Qiyue Liang Yuxue Xu Zhaowei Xu Longping Wen Pengfei Wei |
| author_sort | Na Zhang |
| collection | DOAJ |
| description | Mutations in the p53 gene are frequently observed in various cancers, prompting the initiation of efforts to restore p53 function as a therapeutic approach several decades ago. Nevertheless, only a limited number of drug development initiatives have progressed to late-stage clinical trials, and to date, no p53-targeted therapies have received approval in the USA or Europe. This situation can be attributed primarily to the characteristics of p53 as a nuclear transcription factor, which lacks the conventional features associated with drug targets and has historically been considered “undruggable”. In recent years, however, several promising strategies have emerged, including the enhanced iterations of previous approaches and novel techniques aimed at targeting proteins that have traditionally been considered undruggable. There is a growing interest in small molecules that can restore the tumor-suppressive functions of mutant p53 proteins, and the development of drugs specifically designed for particular p53 mutation types is currently underway. Other approaches aim to deplete mutant p53 or exploit vulnerabilities associated with its expression. Additionally, genetic therapy strategy and approaches have rekindled interest. Advances in mutant p53 biology, compound mechanisms, treatment modalities, and nanotechnology have opened up new avenues for p53-based therapies. However, significant challenges remain in clinical development. This review reassesses the progress in targeting p53-mutant cancers, discusses the obstacles in translating these approaches into effective therapies, and highlights p53-based therapies via nanotechnology. |
| format | Article |
| id | doaj-art-32e72ee69f384841ad8f8b9e5cbd19fb |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-32e72ee69f384841ad8f8b9e5cbd19fb2025-08-20T03:27:18ZengMDPI AGBiomolecules2218-273X2025-05-0115676310.3390/biom15060763Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated CancersNa Zhang0Zhiyuan Jing1Jie Song2Qiyue Liang3Yuxue Xu4Zhaowei Xu5Longping Wen6Pengfei Wei7Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaShandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaShandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaShandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaShandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaShandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaGuangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, ChinaShandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaMutations in the p53 gene are frequently observed in various cancers, prompting the initiation of efforts to restore p53 function as a therapeutic approach several decades ago. Nevertheless, only a limited number of drug development initiatives have progressed to late-stage clinical trials, and to date, no p53-targeted therapies have received approval in the USA or Europe. This situation can be attributed primarily to the characteristics of p53 as a nuclear transcription factor, which lacks the conventional features associated with drug targets and has historically been considered “undruggable”. In recent years, however, several promising strategies have emerged, including the enhanced iterations of previous approaches and novel techniques aimed at targeting proteins that have traditionally been considered undruggable. There is a growing interest in small molecules that can restore the tumor-suppressive functions of mutant p53 proteins, and the development of drugs specifically designed for particular p53 mutation types is currently underway. Other approaches aim to deplete mutant p53 or exploit vulnerabilities associated with its expression. Additionally, genetic therapy strategy and approaches have rekindled interest. Advances in mutant p53 biology, compound mechanisms, treatment modalities, and nanotechnology have opened up new avenues for p53-based therapies. However, significant challenges remain in clinical development. This review reassesses the progress in targeting p53-mutant cancers, discusses the obstacles in translating these approaches into effective therapies, and highlights p53-based therapies via nanotechnology.https://www.mdpi.com/2218-273X/15/6/763mutant p53mutant p53 reactivationprotein stabilitynanodelivery |
| spellingShingle | Na Zhang Zhiyuan Jing Jie Song Qiyue Liang Yuxue Xu Zhaowei Xu Longping Wen Pengfei Wei Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated Cancers Biomolecules mutant p53 mutant p53 reactivation protein stability nanodelivery |
| title | Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated Cancers |
| title_full | Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated Cancers |
| title_fullStr | Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated Cancers |
| title_full_unstemmed | Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated Cancers |
| title_short | Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated Cancers |
| title_sort | discovery of drugs targeting mutant p53 and progress in nano enabled therapeutic strategy for p53 mutated cancers |
| topic | mutant p53 mutant p53 reactivation protein stability nanodelivery |
| url | https://www.mdpi.com/2218-273X/15/6/763 |
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