Novel targeted agents in Her-2 positive and triple negative breast cancer

作者: Dimitrios Tryfonopoulos

DOI:

关键词: Targeted therapyBreast cancerDasatinibMedicineInternal medicineCancerSunitinibOncologyTriple-negative breast cancerSunitinib malateTrastuzumab

摘要: The development of Her-2 targeted therapies has improved the prognosis for patients with positive breast cancer. However, not all tumours respond to treatment antagonists. Triple negative cancers are resistant hormone and therapies. This project focused on improving response in overexpressing cancer developing effective therapy strategies triple cancer. We tested a number multi-target kinase inhibitors (imatinib, sunitinib, pazopanib dasatinib) cell lines, alone combination other agents. Two lines showed moderate sensitivity sunitinib malate. Combined trastuzumab compared either drug alone, four tested. Dasatinib inhibited growth 3 5 but only 1 4 tested. Based inhibitors, which have overlapping target specificities, Src,PP2, our results suggest that dasatinib is due inhibition ephrin type A receptors. Consistent this hypothesis, neither Src expression nor phosphorylation predicted dasatinib, high levels Ephrin receptor 2 protein correlated sensitivity. High caveolin also panel lines. Dasatinib combined cisplatin was synergistic three dasatinib-sensitive lines. Dasatinib, 5’-deoxy-5’-fluoruridine, displayed synergy or additivity. Moderate observed docetaxel two In conclusion, we identified as rational testing triple-negative cancer, putative predictive biomarkers (EphA2, CAV1 CAV2).

参考文章(107)
C K Baumann, M Castiglione-Gertsch, Clinical use of selective estrogen receptor modulators and down regulators with the main focus on breast cancer. Minerva ginecologica. ,vol. 61, pp. 517- 539 ,(2009)
Irene V. Bijnsdorp, Elisa Giovannetti, Godefridus J. Peters, Analysis of Drug Interactions Methods of Molecular Biology. ,vol. 731, pp. 421- 434 ,(2011) , 10.1007/978-1-61779-080-5_34
Elizabeth A. Comen, Mark Robson, Inhibition of poly(ADP)-ribose polymerase as a therapeutic strategy for breast cancer. Oncology. ,vol. 24, pp. 55- 62 ,(2010)
Nicholas Turner, Andrew Tutt, Alan Ashworth, Hallmarks of 'BRCAness' in sporadic cancers Nature Reviews Cancer. ,vol. 4, pp. 814- 819 ,(2004) , 10.1038/NRC1457
C.J. Vlahos, W.F. Matter, K.Y. Hui, R.F. Brown, A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). Journal of Biological Chemistry. ,vol. 269, pp. 5241- 5248 ,(1994) , 10.1016/S0021-9258(17)37680-9
Addolorata Maria Luce Coluccia, Teresa Cirulli, Paola Neri, Domenica Mangieri, Maria Cristina Colanardi, Antonio Gnoni, Nicola Di Renzo, Franco Dammacco, Pierfrancesco Tassone, Domenico Ribatti, Carlo Gambacorti-Passerini, Angelo Vacca, Validation of PDGFRβ and c-Src tyrosine kinases as tumor/vessel targets in patients with multiple myeloma: preclinical efficacy of the novel, orally available inhibitor dasatinib Blood. ,vol. 112, pp. 1346- 1356 ,(2008) , 10.1182/BLOOD-2007-10-116590
Amparo Palmer, Manuel Zimmer, Kai S Erdmann, Volker Eulenburg, Annika Porthin, Rolf Heumann, Urban Deutsch, Rüdiger Klein, EphrinB Phosphorylation and Reverse Signaling Molecular Cell. ,vol. 9, pp. 725- 737 ,(2002) , 10.1016/S1097-2765(02)00488-4
Nicole Dodge Zantek, Michael S. Kinch, Daniel P. Zelinski, Jane C. Stewart, Armando R. Irizarry, EphA2 overexpression causes tumorigenesis of mammary epithelial cells Cancer Research. ,vol. 61, pp. 2301- 2306 ,(2001)
Rita Nahta, Francisco J Esteva, HER2 therapy: Molecular mechanisms of trastuzumab resistance Breast Cancer Research. ,vol. 8, pp. 215- 215 ,(2006) , 10.1186/BCR1612