Anti-proliferative effect of lapatinib in HER2-positive and HER2-negative/HER3-high breast cancer: results of the pre-surgical randomized MAPLE trial (CRUK E/06/039)Alexandra Leary,
نویسندگان
چکیده
1 Institut de Cancerologie, Gustave Roussy, France 2 Poole Hospital NHS Foundation Trust, Poole, UK 3 The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, UK 4 The Institute of Cancer Research – Clinical Trials and Statistics Unit, Division of Clinical Studies, Sutton, UK 5 DNA Electronics Ltd, London, UK 6 Academic Department of Biochemistry, Royal Marsden NHS Foundation Trust, London, UK 7 Maidstone and Tunbridge Wells NHS Foundation Trust, Kent, UK 8 University Hospital of South Manchester NHS Foundation Trust, Manchester, UK
منابع مشابه
Antiproliferative Effect of Lapatinib in HER2-Positive and HER2-Negative/HER3-High Breast Cancer: Results of the Presurgical Randomized MAPLE Trial (CRUK E/06/039).
PURPOSE Not all breast cancers respond to lapatinib. A change in Ki67 after short-term exposure may elucidate a biomarker profile for responsive versus nonresponsive tumors. EXPERIMENTAL DESIGN Women with primary breast cancer were randomized (3:1) to 10 to 14 days of preoperative lapatinib or placebo in a multicenter phase II trial (ISRCTN68509377). Biopsies pre-/posttreatment were analyzed ...
متن کاملPersonalized Medicine and Imaging Antiproliferative Effect of Lapatinib in HER2-Positive and HER2-Negative/HER3-High Breast Cancer: Results of the Presurgical Randomized MAPLE Trial (CRUK E/06/039)
Purpose: Not all breast cancers respond to lapatinib. A change in Ki67 after short-term exposure may elucidate a biomarker profile for responsive versus nonresponsive tumors. ExperimentalDesign:Womenwith primary breast cancerwere randomized (3:1) to 10 to 14 days of preoperative lapatinib or placebo in a multicenter phase II trial (ISRCTN68509377). Biopsies pre-/posttreatment were analyzed for ...
متن کاملHeregulin-expressing HER2-positive breast and gastric cancer exhibited heterogeneous susceptibility to the anti-HER2 agents lapatinib, trastuzumab and T-DM1
BACKGROUND Overexpression of heregulin, a HER3 ligand, is one mechanism that confers resistance to the anti-HER2 agents trastuzumab and lapatinib. We investigated the impact of heregulin expression on the efficacy of HER2-targeted therapeutic agents, including trastuzumab, trastuzumab emtansine (T-DM1) and lapatinib, in vitro and in vivo and evaluated the heregulin messenger RNA (mRNA) levels i...
متن کاملCancer Therapy: Preclinical Dual Blockade of HER2 inHER2-Overexpressing TumorCells Does Not Completely Eliminate HER3 Function
Purpose: Dual blockade of HER2 with trastuzumab and lapatinib or with pertuzumab is a superior treatment approach compared with single-agent HER2 inhibitors. However, many HER2-overexpressing breast cancers still escape from this combinatorial approach. Inhibition of HER2 and downstream phosphoinositide 3-kinase (PI3K)/AKT causes a transcriptional and posttranslational upregulation of HER3 whic...
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...
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