Dual mTOR Kinases MLN0128 Inhibitor Sensitizes HR+/HER2+ Breast Cancer Patient-derived Xenografts to Trastuzumab or Fulvestrant
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منابع مشابه
Combined treatment with everolimus and fulvestrant reversed anti-HER2 resistance in a patient with refractory advanced breast cancer: a case report
BACKGROUND Everolimus, an inhibitor of the mammalian target of rapamycin, shows promising antitumor activity when combined with trastuzumab and chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer or when combined with endocrine agents for hormone receptor (HR)-positive tumors. However, data are limited regarding the effect of everolimus in combination with en...
متن کاملLow-scale phosphoproteome analyses identify the mTOR effector p70 S6 kinase 1 as a specific biomarker of the dual-HER1/HER2 tyrosine kinase inhibitor lapatinib (Tykerb) in human breast carcinoma cells.
BACKGROUND Discovery of key proliferative and/or survival cascades closely linked to the biological effects of human epidermal growth factor receptor (HER) 1 (erbB-1) and/or HER2 (erbB-2) inhibitors may identify a priori mechanisms responsible for the development of acquired resistance in breast cancer disease. Here, we took advantage of a semiquantitative protein array technology to identify i...
متن کاملDual mTORC1/2 and HER2 blockade results in antitumor activity in preclinical models of breast cancer resistant to anti-HER2 therapy.
PURPOSE The PI3K/Akt/mTOR pathway is an attractive target in HER2-positive breast cancer that is refractory to anti-HER2 therapy. The hypothesis is that the suppression of this pathway results in sensitization to anti-HER2 agents. However, this combinatorial strategy has not been comprehensively tested in models of trastuzumab and lapatinib resistance. EXPERIMENTAL DESIGN We analyzed in vitro...
متن کاملAn Experimental Analysis of the Molecular Effects of Trastuzumab (Herceptin) and Fulvestrant (Falsodex), as Single Agents or in Combination, on Human HR+/HER2+ Breast Cancer Cell Lines and Mouse Tumor Xenografts
PURPOSE To investigate the effects of trastuzumab (herceptin) and fulvestrant (falsodex) either in combination or alone, on downstream cell signaling pathways in lab-cultured human HR+/HER2+ breast cancer cell lines ZR-75-1 and BT-474, as well as on protein expression levels in mouse xenograft tissue. METHODS Cells were cultivated in the presence of trastuzumab or fulvestrant or both. Molecul...
متن کاملHuman breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network.
PURPOSE We have investigated mechanisms of acquired resistance to the HER2 antibody trastuzumab in BT-474 human breast cancer cells. EXPERIMENTAL DESIGN BT-474 xenografts established in athymic nude mice were eliminated by trastuzumab. Continuous cell lines (HR for Herceptin resistant) were generated from tumors that recurred in the presence of continuous antibody therapy. RESULTS The isola...
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تاریخ انتشار 2017