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Disrupting tumor resistance through therapy targeting depletion of Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma patient-derived xenograft

Grant number: 22/01257-4
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2022
Effective date (End): June 30, 2025
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Pablo Agustin Vargas
Grantee:Brendo Vinicius Rodrigues Louredo
Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Head and Neck Squamous Cell Carcinomas (HNSCCs) are the sixth most common Cancer worldwide, with the mouth and oropharynx as the most affected sites. The treatment is complex and involves, in most cases, the use of multiple therapeutic modalities in combination. Chemotherapy, with or without surgery or radiotherapy, has been widely used in advanced cases of HNSCC. However, when compared to other types of Cancer, the treatment response is limited and the main reason of this limitation is based on tumor resistance to chemotherapeutic agents. Resistance to these agents may occur due to intense compaction (hypoacetylation) of chromatin in Cancer Stem Cells (CSCs) and to its accumulation, which can be induced by activation of nuclear Transcription Factor kappa B (NFºB) through phosphorylation of IºB±. It has already been shown that pharmacological acetylation of histones induces a reduction in the number of CSCs. Therefore, the aim of this project is to assess in vivo the effect of Histone Deacetylase inhibitors (HDACi) and selective inhibitors of IºB± phosphorylation (IºB±i; NFºB super repressor) isolated and associated with Cisplatin in the treatment of HNSCC. For this purpose, Tongue Squamous Cell Carcinoma Xenografts from patients and implanted in the dorsum of Nude mice will be submitted to different therapeutic protocols with SAHA (HDACi), Cephalin (IºB±i) and Cisplatin. The outcomes of the therapies will be evaluated through clinical evaluation of the tumors, flow cytometry and mapping of the epigenetic profile of HNSCC (ChIP-seq). We aim to propose a new therapeutic strategy that leads to the clinical reduction of HNSCC, in order to minimize the chances of tumor recurrence and metastases. (AU)

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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)
LOUREDO, BRENDO VINICIUS RODRIGUES; DE OLIVEIRA, MARIA CECILIA QUERIDO; BRANDAO, THAIS BIANCA; MIYAHARA-FELIPE, LEIKA; VARGAS, PABLO AGUSTIN; PRADO-RIBEIRO, ANA CAROLINA. The first case report of metastatic rectal adenocarcinoma to the oral vestibule in a young woman. Oral Oncology, v. 143, p. 4-pg., . (22/01257-4)
BRENDO VINICIUS RODRIGUES LOUREDO; MARIA PAULA CURADO; PAULO VICTOR MENDES PENAFORT; JOSÉ ALCIDES ALMEIDA DE ARRUDA; LUCAS GUIMARÃES ABREU; RICARDO ALVES MESQUITA; DÉCIO DOS SANTOS PINTO-JÚNIOR; ALINE CORRÊA ABRAHÃO; BRUNO AUGUSTO BENEVENUTO DE ANDRADE; MICHELLE AGOSTINI; et al. Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil. Brazilian Oral Research, v. 37, . (22/01257-4)
GIRALDO-ROLDAN, DANIELA; FERNANDES, DIEGO TETZNER; LOUREDO, BRENDO VINICIUS RODRIGUES; PENAFORT, PAULO VICTOR MENDES; ROZA, ANA LUIZA OLIVEIRA CORREA; SANTOS-SILVA, ALAN ROGER; VARGAS, PABLO AGUSTIN. An ulcerative nodule on the dorsal tongue in an 8-year-old boy. ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY, v. 136, n. 2, p. 6-pg., . (22/01257-4, 09/53839-2, 20/03818-8)
CRUZ, VITORIA MARIA SOUSA; PEREZ-DE-OLIVEIRA, MARIA EDUARDA; LEITE, EDER GERARDO DOS SANTOS; LOUREDO, BRENDO VINICIUS RODRIGUES; BEZERRA, HELEN KALINE FARIAS; LOPES, MARCIO AJUDARTE; VARGAS, PABLO AGUSTIN; SANTOS-SILVA, ALAN ROGER; KOWALSKI, LUIZ PAULO; PEREZ, DANYEL ELIAS DA CRUZ. Clinicopathological study and survival outcomes of sialoblastoma: A systematic review. HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, v. 45, n. 8, p. 13-pg., . (22/01257-4, 19/09692-9, 21/10810-6)

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