ARX788, a novel anti-HER2 antibody-drug conjugate, shows anti-tumor effects in preclinical models of trastuzumab emtansine-resistant HER2-positive breast cancer and gastric cancer

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Barok , M , Le Joncour , V , Martins , A , Isola , J , Salmikangas , M , Laakkonen , P & Joensuu , H 2020 , ' ARX788, a novel anti-HER2 antibody-drug conjugate, shows anti-tumor effects in preclinical models of trastuzumab emtansine-resistant HER2-positive breast cancer and gastric cancer ' , Cancer Letters , vol. 473 , pp. 156-163 . https://doi.org/10.1016/j.canlet.2019.12.037

Title: ARX788, a novel anti-HER2 antibody-drug conjugate, shows anti-tumor effects in preclinical models of trastuzumab emtansine-resistant HER2-positive breast cancer and gastric cancer
Author: Barok, Mark; Le Joncour, Vadim; Martins, Ana; Isola, Jorma; Salmikangas, Marko; Laakkonen, Pirjo; Joensuu, Heikki
Contributor: University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, Department of Oncology
University of Helsinki, Helsinki Institute of Life Science HiLIFE
University of Helsinki, Research Programs Unit
Date: 2020
Language: eng
Number of pages: 8
Belongs to series: Cancer Letters
ISSN: 0304-3835
URI: http://hdl.handle.net/10138/313125
Abstract: The majority of HER2-positive breast or gastric cancers treated with T-DM1 eventually show resistance to this agent. We compared the effects of T-DM1 and ARX788, a novel anti-HER2 antibody-drug conjugate, on cell growth and apoptosis in HER2-positive breast cancer and gastric cancer cell lines sensitive to T-DM1, gastric cancer cell lines resistant to T-DM1, HER2-negative breast cancer cell lines, and T-DM1-resistant xenograft models. ARX788 was effective in T-DM1-resistant in vitro and in vivo models of HER2-positive breast cancer and gastric cancer. ARX788 showed a pronounced growth inhibitory effect on all five HER2-positive cell lines tested, of which two gastric cancer cell lines had acquired resistance to T-DM1. ARX788 evoked more apoptotic events compared to T-DM1. While JIMT-1 and RN-87 xenograft tumors progressed on T-DM1 treatment, all such tumors responded to ARX788, and four out of the six JIMT-1 tumors and nine out of the twelve RN-87 tumors disappeared during the ARX788 treatment. Mice treated with ARX788 survived longer than those treated with T-DM1. The data support evaluation of ARX788 in patients with HER2-positive breast cancer or gastric cancer including cancers that progress during T-DM1 therapy.
Subject: Human epidermal growth factor receptor 2
T-DM1
Xenograft
Apoptosis
Drug resistance
PLUS
HER2
3122 Cancers
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