Investigation of new therapeutic targets from transcriptional networks of genes of the mitotic spindle associated with embryonic developmental pathways in the ependymoma: focus on molecular subgroups of worst outcome

• Grant number: 16/19820-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2017
• End date: April 30, 2020
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Luiz Gonzaga Tone
• Grantee: Taciani de Almeida Magalhães
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/20341-0 - Interactions between emerging therapeutic targets and developmental pathways associated with tumorigenesis: emphasis on pediatric malignancies, AP.TEM
• Associated scholarship(s): 18/18842-1 - The role of the Hedgehog signaling pathway in ependymoma, BE.EP.DR

Abstract

The ependymoma (EPN) is the third brain tumor most frequently in children, however it can also affect adolescents and adults. Despite the standard treatment (surgical resection followed by radiotherapy), about 50% of the patients with this kind of tumor die due resistance to therapies and local tumor recurrence. Because of this fact, genomic methods of high-throughput and computational approaches can allow the discovery of molecular targets more specific for therapy of ependymal tumors of worst outcome, since these approaches enable the survey of complex molecular interations, modeling them as interaction networks. In these search of new targets, highlight the proteins of mitotic spindle, as for example the proteins MAD and BUB, as well as CDKs, PLKs and AURKs, which are involved with chromsomic alterations and tumorigenesis of several tumors. However, the lack of reports that detail the role of these proteins in the EPN. Recent studies also suggest that these proteins can be involved with the regulation of developmental pathways Wnt, Notch and Shh during the progression of several tumors. Nevertheless, it has not been found studies reporting the interaction of proteins with developmental pathways in EPN. In this context, we think the proteins of mitotic spindle may be associated with the developmental pathways during tumorigenesis of EPN subgroup of worst outcome. Therefore, the research proposal of this project is identify transcriptional networks of genes of the mitotic spindle associated with one or more developmental pathways of the ependymal tumors of worst outcome. This investigation will be able to provide new molecular perspectives to the identification of outcome markers and new therapeutic strategies (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)

MAGALHAES, TACIANI DE ALMEIDA; BORGES, KLEITON SILVA; DE SOUSA, GRAZIELLA RIBEIRO; BRANDALISE, SILVIA REGINA; SEIDINGER, ANA LUIZA; SCRIDELI, CARLOS ALBERTO; OBA-SHINJO, SUELI MIEKO; YUNES, JOSE ANDRES; TONE, LUIZ GONZAGA. The TP53 p.R337H mutation is uncommon in a Brazilian cohort of pediatric patients diagnosed with ependymoma. NEUROLOGICAL SCIENCES, v. 41, n. 3, p. 691-694, MAR 2020. (16/19820-6, 14/20341-0, 15/03614-5)

MAGALHAES, TACIANI DE ALMEIDA; VEIGA CRUZEIRO, GUSTAVO ALENCASTRO; DE SOUSA, GRAZIELLA RIBEIRO; ENGLINGER, BERNHARD; PEINADO NAGANO, LUIS FERNANDO; ANCLIFFE, MATHEW; DA SILVA, KETERYNE RODRIGUES; JIANG, LI; GOJO, JOHANNES; LIU, YULU CHERRY; et al. Activation of Hedgehog signaling by the oncogenic RELA fusion reveals a primary cilia-dependent vulnerability in supratentorial ependymoma. NEURO-ONCOLOGY, v. 25, n. 1, p. 14-pg., 2022-05-31. (18/18842-1, 16/19820-6, 14/20341-0)

MAGALHAES, TACIANI DE ALMEIDA; DE SOUSA, GRAZIELLA RIBEIRO; CRUZEIRO, GUSTAVO ALENCASTRO VEIGA; TONE, LUIZ GONZAGA; VALERA, ELVIS TERCI; BORGES, KLEITON SILVA. The therapeutic potential of Aurora kinases targeting in glioblastoma: from preclinical research to translational oncology. JOURNAL OF MOLECULAR MEDICINE-JMM, v. 98, n. 4, MAR 2020. (17/06511-8, 16/19820-6, 18/23372-4)