Oncotarget, 2016-07, Vol.7 (28), p.42859-42872
2016
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- Autor(en) / Beteiligte
- Titel
- Integrated in vivo genetic and pharmacologic screening identifies co-inhibition of EGRF and ROCK as a potential treatment regimen for triple-negative breast cancer
- Ist Teil von
- Oncotarget, 2016-07, Vol.7 (28), p.42859-42872
- Ort / Verlag
- United States: Impact Journals LLC
- Erscheinungsjahr
- 2016
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Breast cancer is the second most common cause of cancer-related deaths worldwide among women. Despite several therapeutic options, 15% of breast cancer patients succumb to the disease owing to tumor relapse and acquired therapy resistance. Particularly in triple-negative breast cancer (TNBC), developing effective treatments remains challenging owing to the lack of a common vulnerability that can be exploited by targeted approaches. We have previously shown that tumor cells have different requirements for growth in vivo than in vitro. Therefore, to discover novel drug targets for TNBC, we performed parallel in vivo and in vitro genetic shRNA dropout screens. We identified several potential drug targets that were required for tumor growth in vivo to a greater extent than in vitro. By combining pharmacologic inhibitors acting on a subset of these candidates, we identified a synergistic interaction between EGFR and ROCK inhibitors. This combination effectively reduced TNBC cell growth by inducing cell cycle arrest. These results illustrate the power of in vivo genetic screens and warrant further validation of EGFR and ROCK as combined pharmacologic targets for breast cancer.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1949-2553eISSN: 1949-2553DOI: 10.18632/oncotarget.10230Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5189992
- Format
- –
- Schlagworte
- Animals, Cell Line, Tumor, Cell Proliferation - genetics, Drug Synergism, ErbB Receptors - antagonists & inhibitors, ErbB Receptors - genetics, ErbB Receptors - metabolism, Female, HEK293 Cells, Humans, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Priority Research Paper, Protein Kinase Inhibitors - pharmacology, rho-Associated Kinases - antagonists & inhibitors, rho-Associated Kinases - genetics, rho-Associated Kinases - metabolism, RNA Interference, Triple Negative Breast Neoplasms - drug therapy, Triple Negative Breast Neoplasms - genetics, Triple Negative Breast Neoplasms - metabolism, Xenograft Model Antitumor Assays - methods