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Advisor(s)
Abstract(s)
ABSTRACT - Feline mammary carcinoma (FMC) is a highly prevalent tumor, showing aggressive
clinicopathological features, with HER2-positive being the most frequent subtype. While, in human
breast cancer, the use of anti-HER2 monoclonal antibodies (mAbs) is common, acting by blocking the
extracellular domain (ECD) of the HER2 protein and by inducing cell apoptosis, scarce information
is available on use these immunoagents in FMC. Thus, the antiproliferative effects of two mAbs
(trastuzumab and pertuzumab), of an antibody–drug conjugate compound (T-DM1) and of combined
treatments with a tyrosine kinase inhibitor (lapatinib) were evaluated on three FMC cell lines (CATMT, FMCm and FMCp). In parallel, the DNA sequence of the her2 ECD (subdomains II and IV) was
analyzed in 40 clinical samples of FMC, in order to identify mutations, which can lead to antibody
resistance or be used as prognostic biomarkers. Results obtained revealed a strong antiproliferative
effect in all feline cell lines, and a synergistic response was observed when combined therapies were
performed. Additionally, the mutations found were not described as inducing resistance to therapy
in breast cancer patients. Altogether, our results suggested that anti-HER2 mAbs could become
useful in the treatment of FMC, particularly, if combined with lapatinib, since drug-resistance seems
to be rare.
Description
Research Areas: Oncology
Keywords
Feline mammary carcinoma HER2 Monoclonal antibodies Combined therapies Tyrosine Kinase inhibitors Feline her2 mutations
Pedagogical Context
Citation
Gameiro A, Nascimento C, Correia J, Ferreira F. 2021. HER2-Targeted immunotherapy and combined protocols showed promising antiproliferative effects in feline mammary carcinoma cell-based models. Cancers 13(9):2007. Doi: 10.3390/cancers13092007
Publisher
MDPI