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Cancer is responsible for 13% of deaths worldwide and it is the second leading cause of mortality, especially in developing countries. Among the different types of cancer, squamous cell carcinoma of the head and neck (HNSCC) is a disease with high incidence and mortality. The major reasons for this high mortality stand out in the late detection, in the failure in the first treatment approach and in the frequent development of loco-regional recurrences; factors that contribute to an 5-year overall survival of 50%. The therapeutic strategy choice to be adopted in the treatment of HNSCC is based on tumor location and TNM staging system. However, in many cases, tumors with same clinical stage and location and treated by the same method exhibit different patterns of recurrence and mortality. Therefore, there is a need for new tools that could be useful to help in the prognosis determination, in the definition of the therapeutic approach and in the development of new and effective forms of treatment.The radiotherapy (RT) is widely used in the treatment of early cases of HNSCC, but in general 20-30% of patients do not respond to RT. Currently, there are no indicators able to predict which tumors are likely to respond to RT and which ones will be tough and will persist. Therefore, it is necessary to find new markers to discriminate, in advance, which patients may take benefit from treatment with RT.It is known that mammalian cells, including cancer cells, secrete extracellular vesicles (EV) carrying proteins, gene transcripts and microRNAs. These EVs are secreted by many cell types and are present in body fluids (plasma, saliva, urine, etc.). The hypothesis presented in subproject 1 assumes that EVs present in the plasma of patients with HNSCC may contain specific molecules that can be useful for predicting the response at RT. So, when comparing the content of EVs extracted from plasma of HNSCC patients it would be able to discriminate tumors from RT responders and non-responder ones.The main goal of subproject 2 is to identify microRNAs that may distinguish radioresistant larynx tumor from those radiosensitive. For this reason, the microRNAs expression profile of radioresistant and radiosensitive tumors will be compared and differentially expressed candidates will be selected. These candidates will be validated in an independent cohort of initial laryngeal tumors (radioresistant and radiosensitive).The approach proposed in subproject 3 aims to assess the contribution of Cancer/ Testis antigens (CTAs) to the HNSCC tumorigenesis. These antigens, peptides whose expression is restricted to tumor and germline cells, have been identified in different human tumors, however, little information about their influence in the HNSCC are available. Thus, this subproject aims to identify CTAs expressed in HNSCC, verify their relevance as prognostic markers and, through functional studies, envision the contribution of these peptides in the carcinogenesis of HNSCC.Therefore, this project aims the identification of new prognostic markers for HNSCC, which could help in establishment of the better therapeutic approaches, contributing to improvements in the survival rates and in the life quality of patients. The results of this study may also contribute to the discovery of new therapeutic targets, which, in the future, could be useful for the development of new treatment schemes (AU)

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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)
RODRIGUES-JUNIOR, DORIVAL MENDES; RAMINELLI, CRISTIANO; HASSANIE, HAIFA; GOULART TROSSINI, GUSTAVO HENRIQUE; PERECIM, GIVAGO PRADO; CAJA, LAIA; MOUSTAKAS, ARISTIDIS; VETTORE, ANDRE LUIZ. Aporphine and isoquinoline derivatives block glioblastoma cell stemness and enhance temozolomide cytotoxicity. SCIENTIFIC REPORTS, v. 12, n. 1, p. 17-pg., . (20/12530-8, 15/09182-0)
RODRIGUES-JUNIOR, DORIVAL MENDES; TAN, SOON SIM; LIM, SAI KIANG; VIANA, LUCIANO DE SOUZA; CARVALHO, ANDRE LOPES; VETTORE, ANDRE LUIZ; IYER, N. GOPALAKRISHNA. High expression of MLANA in the plasma of patients with head and neck squamous cell carcinoma as a predictor of tumor progression. HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, v. 41, n. 5, p. 1199-1205, . (15/09182-0, 15/21420-3)
RODRIGUES-JUNIOR, DORIVAL MENDES; DE ANDRADE PELARIN, MARIA FERNANDA; NADER, HELENA BONCIANI; VETTORE, ANDRE LUIZ; SILVA PINHAL, MARIA APARECIDA. MicroRNA-1252-5p Associated with Extracellular Vesicles Enhances Bortezomib Sensitivity in Multiple Myeloma Cells by Targeting Heparanase. ONCOTARGETS AND THERAPY, v. 14, p. 455-467, . (15/09182-0, 16/01357-8, 15/03964-6)

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