Rezatapopt: A promising small-molecule “refolder” specific for TP53Y220C mutant tumors
Inactivation of p53 due to mutation is observed in approximately half of all human cancer cases, therefore, restoration of the tumor suppressor function of oncogenic p53 mutants represents an attractive and rational therapeutic approach. Currently, multiple mutant p53 reactivators have been develope...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558625000818 |
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| author | Kostas A. Papavassiliou Alice G. Vassiliou Athanasios G. Papavassiliou |
| author_facet | Kostas A. Papavassiliou Alice G. Vassiliou Athanasios G. Papavassiliou |
| author_sort | Kostas A. Papavassiliou |
| collection | DOAJ |
| description | Inactivation of p53 due to mutation is observed in approximately half of all human cancer cases, therefore, restoration of the tumor suppressor function of oncogenic p53 mutants represents an attractive and rational therapeutic approach. Currently, multiple mutant p53 reactivators have been developed, but only a handful have entered clinical trials [1]. PC14586 (rezatapopt) is an orally available small-molecule reactivator of the Y220C-mutant p53 protein that showed preliminary efficacy and a favorable safety profile in a phase I clinical trial [2] and is now undergoing evaluation in a phase II clinical trial in patients with advanced solid tumors harboring the TP53Y220C mutation (NCT04585750). Although rezatapopt and other p53 mutant reactivators are under clinical assessment, there are still many knowledge gaps that need to be filled to unleash their full therapeutic potential.The preclinical data presented in a recently published research article by Puzio-Kuter et al. achieve to enhance our understanding of the mechanisms and effects of p53-Y220C reactivator compounds and underscore the potential of targeting p53 mutants in cancer therapy [3]. Through this spotlight article, we aim to summarize the findings and emphasize the clinical implications of the study by Puzio-Kutler et al. |
| format | Article |
| id | doaj-art-bf42f53de9404f4caabdcae1703e9f60 |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-bf42f53de9404f4caabdcae1703e9f602025-08-20T03:35:18ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-09-016710120110.1016/j.neo.2025.101201Rezatapopt: A promising small-molecule “refolder” specific for TP53Y220C mutant tumorsKostas A. Papavassiliou0Alice G. Vassiliou1Athanasios G. Papavassiliou2First University Department of Respiratory Medicine, ‘Sotiria’ Chest Hospital, Medical School, National and Kapodistrian University of Athens, Athens, GreeceFirst Department of Critical Care Medicine, 'Evangelismos' Hospital, Medical School, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Corresponding author.Inactivation of p53 due to mutation is observed in approximately half of all human cancer cases, therefore, restoration of the tumor suppressor function of oncogenic p53 mutants represents an attractive and rational therapeutic approach. Currently, multiple mutant p53 reactivators have been developed, but only a handful have entered clinical trials [1]. PC14586 (rezatapopt) is an orally available small-molecule reactivator of the Y220C-mutant p53 protein that showed preliminary efficacy and a favorable safety profile in a phase I clinical trial [2] and is now undergoing evaluation in a phase II clinical trial in patients with advanced solid tumors harboring the TP53Y220C mutation (NCT04585750). Although rezatapopt and other p53 mutant reactivators are under clinical assessment, there are still many knowledge gaps that need to be filled to unleash their full therapeutic potential.The preclinical data presented in a recently published research article by Puzio-Kuter et al. achieve to enhance our understanding of the mechanisms and effects of p53-Y220C reactivator compounds and underscore the potential of targeting p53 mutants in cancer therapy [3]. Through this spotlight article, we aim to summarize the findings and emphasize the clinical implications of the study by Puzio-Kutler et al.http://www.sciencedirect.com/science/article/pii/S1476558625000818Cell-cycle progressionImmune checkpoint inhibitorp53-Y220C reactivatorRezatapoptTumor growth inhibition |
| spellingShingle | Kostas A. Papavassiliou Alice G. Vassiliou Athanasios G. Papavassiliou Rezatapopt: A promising small-molecule “refolder” specific for TP53Y220C mutant tumors Neoplasia: An International Journal for Oncology Research Cell-cycle progression Immune checkpoint inhibitor p53-Y220C reactivator Rezatapopt Tumor growth inhibition |
| title | Rezatapopt: A promising small-molecule “refolder” specific for TP53Y220C mutant tumors |
| title_full | Rezatapopt: A promising small-molecule “refolder” specific for TP53Y220C mutant tumors |
| title_fullStr | Rezatapopt: A promising small-molecule “refolder” specific for TP53Y220C mutant tumors |
| title_full_unstemmed | Rezatapopt: A promising small-molecule “refolder” specific for TP53Y220C mutant tumors |
| title_short | Rezatapopt: A promising small-molecule “refolder” specific for TP53Y220C mutant tumors |
| title_sort | rezatapopt a promising small molecule refolder specific for tp53y220c mutant tumors |
| topic | Cell-cycle progression Immune checkpoint inhibitor p53-Y220C reactivator Rezatapopt Tumor growth inhibition |
| url | http://www.sciencedirect.com/science/article/pii/S1476558625000818 |
| work_keys_str_mv | AT kostasapapavassiliou rezatapoptapromisingsmallmoleculerefolderspecificfortp53y220cmutanttumors AT alicegvassiliou rezatapoptapromisingsmallmoleculerefolderspecificfortp53y220cmutanttumors AT athanasiosgpapavassiliou rezatapoptapromisingsmallmoleculerefolderspecificfortp53y220cmutanttumors |