Epithelial-mesenchymal transition and metabolic homeostasis markers associated with resistance to chemotherapy drug cetuximab and collateral sensitivity to piplartine in head and neck Carcinoma

• Grant number: 21/03647-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2021
• End date: June 30, 2022
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Eloiza Helena Tajara da Silva
• Grantee: Carlos Henrique de Paula Diniz
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

Chemotherapeutic drugs are used to prevent the growth and spread of cancer cells. However, they induce an extreme selective pressure that may result in the selection of resistant subclones. Drug resistance is the biggest problem in cancer therapy today. However, resistance to one drug may come at a cost of increased sensitivity to another drug. This evolutionary process, named collateral sensitivity, can be exploited to control the tumor population and delay resistance. The aim of this project is to evaluate the effect of cetuximab - a chemotherapeutic drug used to treat head and neck squamous cell carcinoma (HNSCC) - on epithelial-mesenchymal transition and metabolic homeostasis and to investigate the collateral sensitivity in resistant cells. The responses to cetuximab treatment in HNSCC cells will be investigated using cell proliferation, lactate production, glucose consumption assays, and gene expression analysis focusing regulators of epithelial-mesenchymal transition and lipid metabolism. To evaluate collateral sensitivity, cetuximab-resistant cells will be treated with piperine, a drug recently studied by us, which is a potential modulator for cancer prevention and progression.(AU)

Scientific publications

(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)

POLACHINI, GIOVANA MUSSI; DE CASTRO, TIALFI BERGAMIN; SMARRA, LUIS FABIANO SOARES; HENRIQUE, TIAGO; DE PAULA, CARLOS HENRIQUE DINIZ; SEVERINO, PATRICIA; LOPEZ, ROSSANA VERONICA MENDOZA; CARVALHO, ANDRE LOPES; DE MATTOS ZERI, ANA CAROLINA; SILVA, ISMAEL DALE COTRIM GUERREIRO; et al. Plasma metabolomics of oral squamous cell carcinomas based on NMR and MS approaches provides biomarker identification and survival prediction. SCIENTIFIC REPORTS, v. 13, n. 1, p. 21-pg., 2023-05-26. (19/07293-0, 21/07087-0, 21/03647-1, 11/23353-0, 10/51168-0)