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Ras signaling activation in acute lymphoblastic leukemia cells

Grant number: 12/08130-8
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): October 01, 2012
Effective date (End): September 30, 2013
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Carlos Alberto Scrideli
Grantee:Vanessa da Silva Silveira
Supervisor abroad: Markus Müschen
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Local de pesquisa : University of California, San Francisco (UCSF), United States  
Associated to the scholarship:10/06067-1 - Effect of the silencing of SHOC2 and XPO7 genes, related to chemotherapy resistance, in acute limphoblastic leukemia cell lines, BP.PD

Abstract

Although the current treatment approach for childhood acute lymphoblastic leukemia (ALL) demonstrate successful rates, some subtypes of the disease remains a major challenge for oncologists. Among these cases are patients who present early resistance to induction chemotherapy. In order to better understand the molecular mechanisms involved in this process, this proposal aims at the investigation of RAS signaling pathway in a new approach: the hyperactivation. Our results so far obtained, show interesting data regarding RAS signaling activation and favorable prognosis, suggesting that this approach may be even more enlightening. Several studies have directed targeted RAS using farnesyl transferase inhibitors as a possible therapeutic approach for treating several types of tumors. However, the data obtained in clinical trials have shown that this approach has had very limited success so far. Therefore, this proposal involves the hyperactivation of RAS signaling pathway by targeting RAS negative regulator, gene NF1, in order to investigate new strategies for the development of therapeutic targets for ALL subsets of early resistance to therapy and consequently highly unfavorable prognosis. This work will contribute significantly to the main post-doctoral project, bringing new perspectives and research approaches. (AU)