Abstract 692: Discovery of novel metformin derivatives with potent antitumor activity in combination with immunotherapy for treatment of triple-negative breast cancer
| Autor: | Vishaka Muhunthan, Begonya Comin-Anduix, Alejandro J. Garcia, Lorena R. Burton, Richard J. Pietras, Gaoyuan Ma, Diana C. Márquez-Garban, Michael E. Jung, Nalo Hamilton, Jennifer M. Murphy, Gang Deng, Cristian D. Yanes, David B. Shackelford |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Cancer Research. 80:692-692 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2020-692 |
| Popis: | Triple negative breast cancer (TNBC) occurs in about 15% of breast cancer (BC) patients, yet it accounts for almost 50% of all BC deaths. TNBC is characterized by lack of expression of estrogen, progesterone and HER2 receptors, and it cannot be treated with current targeted therapies. TNBCs are heterogeneous and occur often in younger and African American women. Although initially responsive to some chemotherapies, TNBCs tend to relapse early and metastasize, leading to poor survival. Development of new therapeutic approaches for clinical translation is a high priority. Emerging evidence from epidemiologic and preclinical work suggests that metformin, the most widely used drug to treat type 2 diabetes mellitus, exerts anticancer activity in BC. Diabetic patients treated with metformin have a reduced incidence and better survival from BC. Moreover, TNBC cells are reported to be uniquely sensitive to metformin in vitro, but strong antitumor effects require relatively high metformin doses in vivo. To address this challenge, we used a structure-activity strategy to develop metformin analogues with more potent anticancer action and safety at lower doses in vivo. Using TNBC cell proliferation in vitro to screen drug candidates, selected new metformin analogues were identified that exerted dose-dependent inhibition of cell proliferation at significantly lower concentrations than that of parental metformin (P Citation Format: Diana C. Márquez-Garban, Gang Deng, Begonya Comin-Anduix, Vishaka Muhunthan, Gaoyuan Ma, Jennifer Murphy, Alejandro J. Garcia, Cristian D. Yanes, Lorena R. Burton, Nalo Hamilton, David Shackelford, Michael E. Jung, Richard J. Pietras. Discovery of novel metformin derivatives with potent antitumor activity in combination with immunotherapy for treatment of triple-negative breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 692. |
| Databáze: | OpenAIRE |
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