Molecular characterization of MTAP (Methylthioadenosine phosphorylase) and evaluation of therapeutic potential in gliomas

• Grant number: 16/06833-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2017
• Effective date (End): October 14, 2018
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Rui Manuel Vieira Reis
• Grantee: Weder Pereira de Menezes
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

Tumors that affect the central nervous system (CNS) correspond to approximately 2% of all malignant types described, however, due to the high mortality, constitute an important public health problem. Among tumors of CNS, gliomas are responsible for approximately 70% of them, that are divided into distinct degrees of malignancy. The grade IV astrocytomas, and glioblastomas (GBM), corresponding to 50% of cases and can manifest at any age, but especially adults. The standard treatment for glioblastoma consists of partial or wide surgical resection, followed by a combined regimen of radiotherapy and adjuvant chemotherapy, especially with temozolomide (TMZ). Despite the therapeutic advance, most cases remain incurables and the inefficiency of clinical results is associated mainly to high infiltration capacity of this tumor type, as well as the intrinsic resistance to drugs used. GBMs are very heterogeneous tumors of the molecular point of view and present several changes, among them, the deletion of the 9p21 region, where is located the tumor suppressor gene, APL (Methylthioadenosine phosphorylase), which operates in the way of polyamines, in recycling of adenine and methionine. The lack of protein may be used as a new strategy of treatment for glioblastomas, using drugs that act on the path of purine de novo synthesis. In this context, the evaluation of the functional effects of the loss of MTAP expression in cell lines GBM as well as the search for new therapeutic approaches such as the combination of specific inhibitors of de novo purine synthesis inhibitors pathway and addition of adjuvants molecules together, is important and can help in knowledge and development of new lines of treatment for patients with this fatal disease. (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)

DE MENEZES, WEDER PEREIRA; OLIVEIRA SILVA, VIVIANE ALINE; FARIA GOMES, IZABELA NATALIA; ROSA, MARCELA NUNES; CORCOLL SPINA, MARIA LUISA; CARLONI, ADRIANA CRUVINEL; VIEIRA ALVES, ANA LAURA; MELENDEZ, MATIAS; ALMEIDA, GISELE CARAVINA; DA SILVA, LUCIANE SUSSUCHI; et al. Loss of 5 `-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness. CELLS, v. 9, n. 2, FEB 2020. (16/18907-0, 17/22305-9, 16/06833-2)

ABRAHAO-MACHADO, LUCAS FARIA; ANTUNES, BRUNO; FILIPPI, RENEE ZON; VOLC, SAHLUA; BOLDRINI, ERICA; MENEZES, WEDER P.; REIS, RUI M.; DE CAMARGO, OLAVO PIRES. Loss of MTAP expression is a negative prognostic marker in Ewing sarcoma family of tumors. BIOMARKERS IN MEDICINE, v. 12, n. 1, p. 35-44, JAN 2018. (16/06833-2)