Abstract 1180: A novel synthetic lethality treatment strategy for metastatic breast cancer
| العنوان: | Abstract 1180: A novel synthetic lethality treatment strategy for metastatic breast cancer |
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| المؤلفون: | Thomas Melendy, Justin Zonneville, Andrei V. Bakin, Christos Fountzilas, Kevin H. Eng, Moyi Wang, Ben Ho Park, Mohammed M. Alruwaili, Renuka Iyer |
| المصدر: | Cancer Research. 81:1180-1180 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, Cell cycle checkpoint, Combination therapy, business.industry, Cancer, Synthetic lethality, medicine.disease, Metastatic breast cancer, Deoxyuridine, chemistry.chemical_compound, Breast cancer, Oncology, chemistry, Cancer cell, medicine, Cancer research, business |
| الوصف: | Breast carcinomas commonly carry mutations in the tumor suppressor p53, while therapeutic efforts to target mutant p53 were largely unfruitful. Here we present preclinical data supporting a novel combination therapy strategy for treatment of p53-deficient cancers. Genomic data revealed a high expression activity of Base-Excision Repair (BER) pathways in p53-deficient breast cancers. However, we found that BER-mediated repair was significantly dysregulated in p53-mutant cancer cells. Treatment with deoxyuridine analogues induced accumulation of DNA damage in p53-mutant cells and inhibitors of poly (ADP-ribose) polymerase (PARPi) greatly enhanced this response. In contrast, normal cells responded to PARPi with activation of the p53-p21 axis and cell cycle arrest. Inactivation of either p53 or p21/CDKN1A in p53 wild-type cells conferred the p53-mutant phenotype. Preclinical breast cancer studies revealed that the combination of deoxyuridine analogue with PARPi was more effective in inhibition of tumor growth and metastases than either drug alone. This work illustrates a novel combination therapy strategy that may improve survival rates and outcomes for thousands of breast cancer patients. Citation Format: Justin Zonneville, Moyi Wang, Mohammed Alruwaili, Kevin Eng, Thomas Melendy, Ben Ho Park, Renuka Iyer, Christos Fountzilas, Andrei V. Bakin. A novel synthetic lethality treatment strategy for metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1180. |
| تدمد: | 1538-7445 0008-5472 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::146b07af24abb6d5ad384b3d5ab898d6 https://doi.org/10.1158/1538-7445.am2021-1180 |
| رقم الأكسشن: | edsair.doi...........146b07af24abb6d5ad384b3d5ab898d6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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