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Using small molecule libraries and high throughput screening to identify new inhibitory compounds to manage mucoepidermoid carcinomas from the salivary glands

Grant number: 21/13381-9
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Start date: July 01, 2022
End date: April 30, 2023
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Pablo Agustin Vargas
Grantee:Luan César da Silva
Supervisor: Rogério Moraes Castilho
Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
Institution abroad: University of Michigan, United States  
Associated to the scholarship:19/06597-5 - Disrupting tumor resistance through therapy targeting depletion of cancer stem cells in Salivary Mucoepidermoid Carcinomas, BP.DR

Abstract

Mucoepidermoid carcinoma (MEC) is the most common malignancy from the salivary glands. The management of MEC follows similar protocols used in other malignancies from the salivary glands. Our previous results presented new therapies that target cancer stem cells (CSC) from MEC. However, new approaches are needed due to radiotherapy toxicities and resistance against the current chemotherapy (Cisplatin), found mainly by CSC. Recently, we demonstrated that epigenetic events have been shown to play an important role in MEC behavior. Based on the current lack of a therapy developed exclusively for MEC, we are proposing to evaluate an Epigenetics Compound Library ("epi-drugs") to identify new pharmacological agents capable of impacting the growth of MEC. Here, we will investigate the "epi-drugs" in 2D and 3D culture models, by High-precision liquid handler and high-throughput assays. Proliferation, migration, and tumorspheres will be evaluated by functional assays. We expect to identify active molecules and define the target population that will most likely benefit from the therapy. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
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Scientific publications
(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)
SILVA, LUAN CESAR; LEITE, AMANDA ALMEIDA; BORGATO, GABRIELL BONIFACIO; WAGNER, VIVIAN PETERSEN; MARTINS, MANOELA DOMINGUES; LOUREIRO, FELIPPE JOSE ALMEIDA; LOPES, MARCIO AJUDARTE; SANTOS-SILVA, ALAN ROGER; SPERANDIO, MARCELO; JUNIOR, GILBERTO DE CASTRO; et al. Oral squamous cell carcinoma cancer stem cells have different drug sensitive to pharmacological NFκB and histone deacetylation inhibition. AMERICAN JOURNAL OF CANCER RESEARCH, v. 13, n. 12, p. 13-pg., . (21/13381-9, 19/06597-5, 16/05710-4)
SILVA, LUAN CESAR; PEREZ-DE-OLIVEIRA, MARIA EDUARDA; PEDROSO, CAIQUE MARIANO; LEITE, AMANDA ALMEIDA; SANTOS-SILVA, ALAN ROGER; LOPES, MARCIO AJUDARTE; DE CASTRO JUNIOR, GILBERTO; MARTINS, MANOELA DOMINGUES; WAGNER, VIVIAN PETERSEN; KOWALSKI, LUIZ PAULO; et al. Systemic therapies for salivary gland carcinomas: an overview of published clinical trials. MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL, v. 29, n. 2, p. 8-pg., . (19/06597-5, 21/10810-6, 21/13381-9, 16/05710-4)
ALMEIDA, LUCIANA O.; SILVA, LUAN CESAR; EMERICK, CAROLINA; DOS SANTOS, JULIANA AMORIM; CASTILHO, ROGERIO M.; SQUARIZE, CRISTIANE H.. Head and neck cancer stem cell maintenance relies on mTOR signaling, specifically involving the mechanistic target of rapamycin complexes 1 and 2 (mTORC1 and mTORC2). ARCHIVES OF ORAL BIOLOGY, v. 157, p. 9-pg., . (21/13381-9, 19/06597-5)