Combined CDK4/6 and PI3Kα Inhibition Is Synergistic and Immunogenic in Triple-Negative Breast Cancer

New treatments for triple-negative breast cancer (TNBC) are urgently needed. Despite there being little evidence of clinical activity as single-agent therapies, we show that dual blockade of PI3Kα and CDK4/6 is synergistically effective against multiple -wild-type TNBC models. Combined PI3Kα and CDK...

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Veröffentlicht in:	Cancer research (Chicago, Ill.) Ill.), 2017-11, Vol.77 (22), p.6340-6352
Hauptverfasser:	Teo, Zhi Ling, Versaci, Stephanie, Dushyanthen, Sathana, Caramia, Franco, Savas, Peter, Mintoff, Chris P, Zethoven, Magnus, Virassamy, Balaji, Luen, Stephen J, McArthur, Grant A, Phillips, Wayne A, Darcy, Phillip K, Loi, Sherene
Format:	Artikel
Sprache:	eng
Schlagworte:	Aminopyridines - administration & dosage Aminopyridines - pharmacology Animal models Animals Antineoplastic Combined Chemotherapy Protocols - pharmacology Antitumor activity Apoptosis Breast cancer Cell activation Cell death Cell Line, Tumor Class I Phosphatidylinositol 3-Kinases - antagonists & inhibitors Class I Phosphatidylinositol 3-Kinases - metabolism CTLA-4 protein Cyclin-dependent kinase 4 Cyclin-Dependent Kinase 4 - antagonists & inhibitors Cyclin-Dependent Kinase 4 - metabolism Cyclin-Dependent Kinase 6 - antagonists & inhibitors Cyclin-Dependent Kinase 6 - metabolism Cytotoxicity Disease control DNA damage Drug Synergism Female Humans Immune checkpoint Immunogenicity Immunomodulation Immunosuppression Inhibition Lymphocytes T Mammary Neoplasms, Experimental - drug therapy Mammary Neoplasms, Experimental - enzymology Mammary Neoplasms, Experimental - immunology Medical treatment Mice, Inbred C57BL Mice, Inbred NOD Mice, Knockout Mice, SCID PD-1 protein Piperazines - administration & dosage Piperazines - pharmacology Purines - administration & dosage Purines - pharmacology Pyridines - administration & dosage Pyridines - pharmacology Suppressor cells Survival Analysis Thiazoles - administration & dosage Thiazoles - pharmacology Triple Negative Breast Neoplasms - drug therapy Triple Negative Breast Neoplasms - enzymology Triple Negative Breast Neoplasms - immunology Tumors Xenograft Model Antitumor Assays Xenografts
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