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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 type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2021
Effective date (End): June 30, 2022
Field of knowledge:Health Sciences - Medicine
Principal researcher:Eloiza Helena Tajara da Silva
Grantee:Carlos Henrique de Paula Diniz
Home 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)

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