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Article

Tyrosine Kinase Inhibitors Are Promising Therapeutic Tools for Cats with HER2-Positive Mammary Carcinoma

1
CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal
2
Antiviral Resistance Laboratory, Infectious Diseases Department, National Institute of Health Dr. Ricardo Jorge, Av. Padre Cruz, 1649-016 Lisbon, Portugal
*
Author to whom correspondence should be addressed.
Academic Editor: Carlos Alonso-Moreno
Received: 16 February 2021 / Revised: 28 February 2021 / Accepted: 2 March 2021 / Published: 6 March 2021
(This article belongs to the Section Drug Targeting and Design)
Feline mammary carcinoma (FMC) is a common neoplasia in cat, being HER2-positive the most prevalent subtype. In woman’s breast cancer, tyrosine kinase inhibitors (TKi) are used as a therapeutic option, by blocking the phosphorylation of the HER2 tyrosine kinase domain. Moreover, clinical trials demonstrated that TKi produce synergistic antiproliferative effects in combination with mTOR inhibitors, overcoming resistance to therapy. Thus, to uncover new chemotherapeutic strategies for cats, the antiproliferative effects of two TKi (lapatinib and neratinib), and their combination with a mTOR inhibitor (rapamycin), were evaluated in FMC cell lines (CAT-M, FMCp and FMCm) and compared with a human breast cancer cell line (SkBR-3). Results revealed that both TKi induced antiproliferative effects in all feline cell lines, by blocking the phosphorylation of EGFR members and its downstream effectors. Furthermore, combined treatments with rapamycin presented synergetic antiproliferative effects. Additionally, the DNA sequence of the her2 TK domain (exons 18 to 20) was determined in 40 FMC tissue samples, and despite several mutations were found none of them were described as inducing resistance to therapy. Altogether, our results demonstrated that TKi and combined protocols may be useful in the treatment of cats with mammary carcinomas, and that TKi-resistant FMC are rare. View Full-Text
Keywords: feline mammary carcinoma; HER2; tyrosine kinase inhibitors; targeted therapies; feline her2 TK mutations feline mammary carcinoma; HER2; tyrosine kinase inhibitors; targeted therapies; feline her2 TK mutations
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MDPI and ACS Style

Gameiro, A.; Almeida, F.; Nascimento, C.; Correia, J.; Ferreira, F. Tyrosine Kinase Inhibitors Are Promising Therapeutic Tools for Cats with HER2-Positive Mammary Carcinoma. Pharmaceutics 2021, 13, 346. https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13030346

AMA Style

Gameiro A, Almeida F, Nascimento C, Correia J, Ferreira F. Tyrosine Kinase Inhibitors Are Promising Therapeutic Tools for Cats with HER2-Positive Mammary Carcinoma. Pharmaceutics. 2021; 13(3):346. https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13030346

Chicago/Turabian Style

Gameiro, Andreia, Filipe Almeida, Catarina Nascimento, Jorge Correia, and Fernando Ferreira. 2021. "Tyrosine Kinase Inhibitors Are Promising Therapeutic Tools for Cats with HER2-Positive Mammary Carcinoma" Pharmaceutics 13, no. 3: 346. https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13030346

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