Scholarship 24/01867-2 - Autofagia, Glioblastoma - BV FAPESP
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Analysis of the impact of autophagy on the response to chemotherapy in glioblastoma

Grant number: 24/01867-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date until: June 01, 2024
End date until: May 31, 2025
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Mariana Lazarini
Grantee:Tainá Lins da Silva
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Glioblastoma is the most aggressive form of brain tumor and is responsible for high rates of morbidity and mortality. In addition to the unfavorable prognosis, the symptoms faced by patients with glioblastoma are challenging and affect not only the individual but also their family members. The standard therapy used to treat glioblastoma consists of surgical resection, followed by radiotherapy and administration of the chemotherapy agent Temozolomide (TMZ). However, this treatment protocol has not been updated since 2005, and resistance to treatment, especially chemotherapy, contributes significantly to high recurrence rates. Autophagy is a mechanism used by cells to maintain cellular homeostasis and is also a strategy used by cancer cells to resist the effects of chemotherapy. In view of this crucial role of autophagy in resistance to chemotherapy in the treatment of glioblastoma, it is important to find ways of modulating this process in order to increase the cytotoxicity of temozolomide in glioblastoma cells and thus improve existing therapies. Although studies have focused on analyzing macroautophagy (MA) and chaperone-mediated autophagy (CMA) separately, it is important to consider the existence of a robust crosstalk between macroautophagy and chaperone-mediated autophagy. Analysis of this crosstalk may be a promising way to improve the ability to modulate autophagy and thus find improvements in the therapeutic outcome of glioblastoma. In this context, the project will use U251 strains knocked out for the ATG7 and LAMP2A genes. In addition, as a disruptive innovation, we intend to establish and validate double knockout cells for ATG7 and LAMP2A, which will allow an in-depth analysis of the interaction between autophagy and response to chemotherapy in glioblastoma.

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