000			nab a22 7a 4500
999			_c17256 _d17256
003			PC17256
005			20230223123913.0
008			230223b xxu||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_91502 _aPérez Núñez, Ángel _eNeurocirugía
100			_93200 _aCantero, Diana _eAnatomía Patológica
100			_9624 _aHernández Laín, Aurelio _e Anatomía Patológica
245	0	0	_aPreclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma. _h[artículo]
260			_bMolecular cancer therapeutics, _c2015
300			_a14(7):1548-58.
500			_aFormato Vancouver: Zahonero C, Aguilera P, Ramírez Castillejo C, Pajares M, Bolós MV, Cantero D et al. Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma. Mol Cancer Ther. 2015 Jul;14(7):1548-58.
501			_aPMID: 25939761
504			_aContiene 40 referencias
520			_aGlioblastomas (GBM) are devastating tumors in which there has been little clinical improvement in the last decades. New molecularly directed therapies are under development. EGFR is one of the most promising targets, as this receptor is mutated and/or overexpressed in nearly half of the GBMs. However, the results obtained with first-generation tyrosine-kinase inhibitors have been disappointing with no clear predictive markers of tumor response. Here, we have tested the antitumoral efficacy of a second-generation inhibitor, dacomitinib (PF299804, Pfizer), that binds in an irreversible way to the receptor. Our results confirm that dacomitinib has an effect on cell viability, self-renewal, and proliferation in EGFR-amplified ± EGFRvIII GBM cells. Moreover, systemic administration of dacomitinib strongly impaired the in vivo tumor growth rate of these EGFR-amplified cell lines, with a decrease in the expression of stem cell-related markers. However, continuous administration of the compound was required to maintain the antitumor effect. The data presented here confirm that dacomitinib clearly affects receptor signaling in vivo and that its strong antitumoral effect is independent of the presence of mutant receptor isoforms although it could be affected by the PTEN status (as it is less effective in a PTEN-deleted GBM line). Dacomitinib is being tested in second line for EGFR-amplified GBMs. We hope that our results could help to select retrospectively molecular determinants of this response and to implement future trials with dacomitinib (alone or in combination with other inhibitors) in newly diagnosed GBMs.
710			_9330 _aServicio de Anatomía Patológica
710			_9312 _aServicio de Neurocirugía
710			_9625 _aInstituto de Investigación imas12
856			_uhttp://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/1/pc17256.pdf _ySolicitar documento
942			_2ddc _cART _n0