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Study of epigenetic modifications related to cancer stem cells accumulation in head and neck cancer: implications in chemoresistance

Grant number: 17/11780-8
Support type:Research Grants - Young Investigators Grants
Duration: February 01, 2018 - January 31, 2022
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Luciana Oliveira de Almeida
Grantee:Luciana Oliveira de Almeida
Home Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Assoc. researchers:Andréia Machado Leopoldino ; Rogerio Moraes Castilho
Associated scholarship(s):19/19045-0 - Epigenetic regulation of head and neck tumors resistant to cisplatin: differences between intrinsic and adquired resistance, BP.IC
19/19301-7 - The role of HDAC6 in the regulation of oxidative stress and chemoresistance of cancer stem cells in oral carcinoma, BP.MS
19/05782-3 - Involvement of NFkB signaling in CSC accumulation of head and neck carcinoma cell lines resistant to chemotherapy, BP.MS
+ associated scholarships 18/17478-4 - Characterization of the mechanism of cancer stem cells accumulation in head and neck squamous carcinoma after chemotherapy, BP.IC
18/13764-2 - Establishment and characterization of head and neck squamous cell carcinoma cell lines resistant to cisplatin, BP.IC
18/02959-7 - Study of epigenetic modifications related to cancer stem cells accumulation in head and neck cancer: implications in chemoresistance, BP.JP - associated scholarships

Abstract

Chemoresistance is a major cause of the failure in the therapy used for the cancer treatment, increasing rates of recurrence and metastasis. It has been suggested that chemoresistance is driven by a small group of cells identified as cancer stem cells. In head and neck cancer, cancer stem cells population is accumulated after chemotherapy e epigenetic modifications may be controlling this process. NFkB pathway has been associated with chemoresistance and its involvement in the epigenetic regulation suggests that NFkB may be modulating cancer stem cells. Thereby, understanding the epigenetic modifications that promote chemoresistance, exploring the behavior of cancer stem cells and the signaling that regulates renewing and differentiation may enable us to modulate epigenetically the cancer stem cells signaling as a therapeutic strategy. Our project aims: (i) identify epigenetic modifications that may be contributing to the chemoresistance of cancer stem cells; (ii) explore the involvement of NFkB protein in the cellular signaling associated with cancer stem cells; (iii) select and characterize the role of genes epigenetically modulated upon cancer stem cells in chemoresistant tumors; (iv) find therapeutic strategies more efficient to ensure the complete abrogation of the cancer stem cells population. We will apply strategies of: stablishment of head and neck cancer cell lines cisplatin-resistant; isolation of cancer stem cell population using flow cytometry assay; identification of gene epigenetically regulated using ATAC-seq, ChIP and MSP; drug screening and in vivo studies using xenograft models. The results will contribute to improve the knowledge about the epigenetic signaling driving the accumulation of chemoresistant cancer stem cells as well as to identify more effective drugs to abbrogate cancer stem cells. (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)
BIGHETTI-TREVISAN, RAYANA L.; SOUSA, LUCAS O.; CASTILHO, ROGERIO M.; ALMEIDA, LUCIANA O. Cancer Stem Cells: Powerful Targets to Improve Current Anticancer Therapeutics. STEM CELLS INTERNATIONAL, v. 2019, NOV 12 2019. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.