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 organization: | CAN-PRO - Translational Cancer Medicine Program Faculty of Medicine University of Helsinki Research Programs Unit Department of Oncology Helsinki Institute of Life Science HiLIFE Pirjo Maarit Laakkonen / Principal Investigator Heikki Joensuu / Principal Investigator HUS Comprehensive Cancer Center |
Date: | 2020 |
Language: | eng |
Number of pages: | 8 |
Belongs to series: | Cancer Letters |
ISSN: | 0304-3835 |
DOI: | https://doi.org/10.1016/j.canlet.2019.12.037 |
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 |
Peer reviewed: | Yes |
Rights: | cc_by_nc_nd |
Usage restriction: | openAccess |
Self-archived version: | acceptedVersion |
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