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Evaluation of RECK and ALX3 expression in cell lines and samples of melanoma patients resistant to vemurafenib (PLX4032) treatment

Grant number: 12/05910-2
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): August 26, 2013
Effective date (End): August 25, 2014
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Silvya Stuchi Maria-Engler
Grantee:Manoela Tiago dos Santos
Supervisor: Keiran Smalley
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University of South Florida (USF), United States  
Associated to the scholarship:11/19045-9 - Methylation of RECK and ALX3 genes in human melanoma, BP.DR


Human melanoma presents extreme chemoresistance and poor prognosis with a high risk of lymph node metastasis, hematogenous, and survival rate of six to nine months. Vemurafenib (PLX4032) caused great impact on therapeutic power because it was capable of inducing arrest of cell cycle and apoptosis , in addition to inhibiting the proliferation exclusively V600E positive cells in vitro systems and in vivo. In patients, there was an 80% reduction of metastatic sites that received a daily administration of PLX4032 with low reported toxicity. Despite the clinical success, most of the observed responses is transient, with relapse and resistance in the majority of cases. The current treatment is therefore still based on the same used in the past decades, even in spite of the evolution therapeutic technology. Understanding the resistance mechanism can provide clues both for developing improved versions of a drug and for guiding the selection of appropriate drug combinations for therapy. Treatment failure is often attributed to the development of chemoresistance. These results suggest that tumor heterogeneity may play especially important in determining responses to dramatic changes in the environment, such as changes induced by anti-cancer therapy. Co-existence of distinct clones within a tumor can have profound clinical implications for disease progression, diagnosis, and therapeutic responses. Therefore, clonal heterogeneity changes in response to chemotherapy needs to be determined for the development of better approaches to treat patients with melanoma. (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)
SANDRI, SILVANA; WATANABE, LUIS R. M.; DE OLIVEIRA, ERICA APARECIDA; FAIAO-FLORES, FERNANDA; MIGLIORINI, SILENE; TIAGO, MANOELA; FELIPE-SILVA, ALOISIO; VAZQUEZ, VINICIUS DE LIMA; SOUZA, PAOLA DA COSTA; LOPES CONSOLARO, MARCIA EDILAINE; et al. Indoleamine 2,3-dioxygenase in melanoma progression and BRAF inhibitor resistance. PHARMACOLOGICAL RESEARCH, v. 159, . (17/04926-6, 17/26148-5, 12/05910-2, 11/19045-9, 16/16554-3, 13/05172-4, 15/10821-7)

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