Combined inhibition of BET proteins AND HDACs as an effective strategy for the treatment of mammary cancer: a comparative study

• Grant number: 19/05778-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: June 18, 2019
• End date: February 17, 2020
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Heidge Fukumasu
• Grantee: Pedro Luiz Porfirio Xavier
• Supervisor: Susanne Muller-Knapp
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Institution abroad: Goethe University Frankfurt, Germany
• Associated to the scholarship: 17/11966-4 - Epigenetic modulations and self-renewal potential of canine mammary cancer cells: the search for potential therapeutic targets, BP.DR

Abstract

Mammary tumors are the most frequent type of cancer in female dogs as in women. Besides that, its cells share similar features and can be used to comparative studies and screening of antineoplastic agents. Epigenetic targets are highlighted as potential and innovative therapy against cancer. Both histone deacetylases (HDACs) and bromodomain and extraterminal proteins (BET) inhibitors have been shown to be efficient in types of cancer such as lymphoma, leukemia and NUT midline carcinomas. In breast cancer, few studies have observed good effects of these inhibitors. Furthermore, when applying individually, some issues may arise, including incomplete efficacy and drug resistance. Thus, new strategies to overcome these limitations are necessary and one of the possibilities is to test the combined effect of HDAC-BET inhibition using a dual inhibitor. We propose, in this Project, an 8-month internship abroad in Buchmann Institute for Molecular Life Sciences at the Goethe University Frankfurt am Main, Germany to test a new and unpublished dual HDAC-BET inhibitor on breast cancer cells using 2D and 3D in vitro models. We believe that the period will be enough to perform the analysis and the data acquired will determine a possible new strategy for future therapies targeting breast cancer. After that, we will observe the effects of the new dual HDAC-BET inhibitor using canine mammary cancer cells from our laboratory in Brazil finding to a comparative approach which will allow us to elucidate a possible treatment strategy for mammary cancer in both women and dogs.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

XAVIER, PEDRO L. P.; CORDEIRO, YONARA G.; ALEXANDRE, PAMELA A.; PIRES, PEDRO R. L.; SARANHOLI, BRUNO H.; SILVA, EDSON R.; MUELLER, SUSANNE; FUKUMASU, HEIDGE. An epigenetic screening determines BET proteins as targets to suppress self-renewal and tumorigenicity in canine mammary cancer cells. SCIENTIFIC REPORTS, v. 9, NOV 22 2019. (17/11966-4, 19/05778-6, 14/02493-7)

RAQUEL LOZANO GUILHARDUCCI; PEDRO LUIZ PORFIRIO XAVIER; JULIANO COELHO DA SILVEIRA; YONARA DE GOUVEIA CORDEIRO; LUIZ ROBERTO BIONDI; RICARDO DE FRANCISCO STREFEZZI; HEIDGE FUKUMASU. Expressão de LIN28A/B e Let-7 miRNAs em carcinomas mamários caninos. Ciência Rural, v. 52, n. 10, 2022-03-14. (14/02493-7, 17/11966-4, 19/05778-6, 15/10036-8)

XAVIER, PEDRO LUIZ PORFIRIO; MUELLER, SUSANNE; FUKUMASU, HEIDGE. Epigenetic Mechanisms in Canine Cancer. FRONTIERS IN ONCOLOGY, v. 10, OCT 23 2020. (19/05778-6, 17/11966-4, 14/02493-7)

SANTOS, MARIANA RODRIGUES; PORFIRIO XAVIER, PEDRO LUIZ; LISBOA PIRES, PEDRO RATTO; ROCHETTI, ARINA LAZARO; ROSIM, DANIELE FERNANDA; SCAGION, GUILHERME PEREIRA; PIRES DE CAMPOS ZUCCARI, DEBORA APARECIDA; MUNIR, MUHAMMAD; FERREIRA, HELENA LAGE; FUKUMASU, HEIDGE. Oncolytic effect of Newcastle disease virus is attributed to interferon regulation in canine mammary cancer cell lines. VETERINARY AND COMPARATIVE ONCOLOGY, v. 19, n. 3, p. 593-601, SEP 2021. (18/06217-5, 19/05778-6, 16/19307-7, 18/06216-9, 14/02493-7)