TP53 mutations, including the TP53 Y220C mutation, are important in cancer

TP53 and cancer

In normal, healthy cells, p53 is a tumor-suppressor protein that monitors for DNA damage and cellular stress, and that can prevent tumor progression.1,2 A mutation in the TP53 gene, which codes for the p53 protein, is commonly found in human cancers and can result in the loss or alteration of normal p53 protein function or a mutated p53 protein.3–6 Mutated p53 protein has an important role in cancer by altering cancer cell gene expression and thereby promoting tumor growth, survival, and progression.1,5,7–9

References: 1. Kastenhuber ER, et al. Cell. 2017;170:1062–1078; 2. Blagih J, et al. J Cell Sci. 2020;133:jcs237453; 3. Levine AJ. Ann Rev Cancer Biol. 2019b;3:21–34; 4. Donehower LA, et al. Cell Rep. 2019;28:1370–1384.e1375; 5. Baugh EH, et al. Cell Death Differ. 2018;25:154–160; 6. Yue X, et al. J Mol Biol. 2017;429:1595–1606; 7. Alexandrova EM, et al. Cell Death Dis. 2017;8:e2661; 8. Mantovani F, et al. Cell Death Differ. 2019;26:199–212; 9. Roszkowska KA, et al. Int J Mol Sci. 2020;21:1334.

The TP53 Y220C mutation causes loss of normal p53 function

The mutated p53 Y220C protein forms a small pocket on the surface of p53 protein, which causes the protein to change its structural shape and lose its ability to bind DNA.1–6 By causing a loss of normal p53 protein function, the mutated p53 Y220C protein can lead to tumor progression and is therefore a potential therapeutic target in certain cancers.4–6

Impact of the TP53 Y220C mutation on the p53 protein

Normal p53 and Y220C mutation

Normal p53 and Y220C mutation

References: 1. Baugh EH, et al. Cell Death Differ. 2018;25:154–160; 2. Roszkowska KA, et al. Int J Mol Sci. 2020;21:1334; 3. Bouaoun L, et al. Hum Mutat. 2016;37:865–876; 4. Blanden AR, et al. Drug Discov Today. 2015;20:1391–1397; 5. Baud MGJ, et al. Eur J Med Chem. 2018;152:101–114; 6. Tang Y, et al. J Phys Chem B. 2021;125:10138–10148.

The TP53 Y220C mutation is found in many types of solid tumors

The TP53 Y220C mutation has been identified in over 30 different solid tumor types.1,2 Across all solid tumors, ovarian cancer has the highest frequency of TP53 Y220C mutations, followed by pancreatic cancer, esophageal cancer, and lung cancer.1 Biomarker testing can identify genomic abnormalities in your tumor profile. Learn more about genes and cancer with the American Cancer Society.3

Frequency of the TP53 Y220C mutation across common solid tumors





Colorectal Cancer




References: 1. Dumbrava EE, et al. Oral presentation at ASCO 2022, Chicago, USA. June 3–7, 2022; 2. Bauer M, et al. Future Med Chem. 2019;11(19):2491–2504; 3. American Cancer Society. Biomarker Tests and Cancer Treatment. Accessed January 2024.


Rezatapopt (also known as PC14586) is being investigated in TP53 Y220C cancer

Rezatapopt is a first-in-class, selective p53 reactivator specific to the mutated p53 Y220C protein.1,2 Rezatapopt is currently under investigation for the treatment of patients with locally advanced or metastatic solid tumors that have a TP53 Y220C mutation (or TP53 Y220C cancer), including but not limited to ovarian cancer, lung cancer, breast cancer and endometrial cancer.3-5

References: 1. The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation. Available at: Accessed January 2024; 2. Joerger AC, et al. Proc Natl Acad Sci U S A. 2006;103:15056–15061; 3. Dumble M, et al. Cancer Res. 2021;81: Abstract LB006; 4. Dumbrava EE, et al. Oral presentation at ASCO 2022, Chicago, USA. June 3–7, 2022; 5. Schram A, et al. Oral presentation at AACR-NCI-EORTC 2023, Boston, USA. October 11–15, 2023.

Further information on clinical studies

Learn more about clinical studies with the National Cancer InstituteAmerican Cancer Society, and European Medicines Agency.

If you are interested in taking part in a clinical trial, the Leal Health service can help find the right trial for you, for free. Click here for more information.

​To learn more about rezatapopt (also known as PC14586) in the PYNNACLE study, please visit

Please contact the PMV Pharmaceuticals Clinical Study Information Center

+1 (609) 235-4038

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Rezatapopt is an investigational agent that has not been approved by the US FDA, EMA or any other regulatory agency for the treatment of cancer.

MA-586-0014 February 2024