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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
- Source :
- Cancer Letters. 473:156-163
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
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.
- Subjects :
- 0301 basic medicine
Human epidermal growth factor receptor 2
Cancer Research
Immunoconjugates
Receptor, ErbB-2
T-DM1
Apoptosis
Drug resistance
Ado-Trastuzumab Emtansine
Mice
chemistry.chemical_compound
Antineoplastic Agents, Immunological
0302 clinical medicine
PLUS
skin and connective tissue diseases
Antibodies, Monoclonal
3. Good health
Oncology
030220 oncology & carcinogenesis
Female
Oligopeptides
musculoskeletal diseases
congenital, hereditary, and neonatal diseases and abnormalities
3122 Cancers
Breast Neoplasms
03 medical and health sciences
Breast cancer
Stomach Neoplasms
In vivo
HER2
Cell Line, Tumor
medicine
Animals
Humans
Cell Proliferation
Cell growth
business.industry
Xenograft
Cancer
medicine.disease
Xenograft Model Antitumor Assays
030104 developmental biology
chemistry
Drug Resistance, Neoplasm
Cell culture
Trastuzumab emtansine
Cancer research
business
Subjects
Details
- ISSN :
- 03043835
- Volume :
- 473
- Database :
- OpenAIRE
- Journal :
- Cancer Letters
- Accession number :
- edsair.doi.dedup.....b7c0e451f0970c70a0b11763c5b668f7