The functional role of p38 MAPK pathway in malignant brain tumors

Nathália Grave; Thamiris Becker Scheffel; Fernanda Fernandes Cruz; Liliana Rockenbach; Márcia Inês Goettert; Stefan Laufer; Fernanda Bueno Morrone

doi:10.3389/fphar.2022.975197

The functional role of p38 MAPK pathway in malignant brain tumors

Front Pharmacol. 2022 Oct 3:13:975197. doi: 10.3389/fphar.2022.975197. eCollection 2022.

Authors

Nathália Grave^{1

2}, Thamiris Becker Scheffel^{2

3}, Fernanda Fernandes Cruz², Liliana Rockenbach^{1

2}, Márcia Inês Goettert^{4

5}, Stefan Laufer⁵, Fernanda Bueno Morrone^{1

2

3}

Affiliations

¹ Programa de Pós-Graduação em Medicina e Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
² Laboratório de Farmacologia Aplicada, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
³ Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
⁴ Laboratorio de Cultura de Células, Programa de Pós-Graduação em Biotecnologia, Universidade do Vale do Taquari (Univates), Lajeado, Brazil.
⁵ Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Eberhard Karls University of Tübingen, Tübingen, Germany.

Abstract

Gliomas are extremely debilitating malignant brain tumors with very limited response to therapies. The initiation and progression of gliomas can be attributed to several molecular abnormalities, such as mutations in important regulatory networks. In this regard, the mitogen-activated protein kinases (MAPKs) arise as key signaling pathways involved in cell proliferation, survival, and differentiation. MAPK pathway has been altered in most glial tumors. In glioma cells, the activation of p38 MAPK contributes to tumor invasion and metastasis and is positively correlated with tumor grade, being considered a potential oncogenic factor contributing to brain tumorigenesis and chemotherapy resistance. Hence, a better understanding of glioma pathogenesis is essential to the advancement of therapies that provide extended life expectancy for glioma patients. This review aims to explore the role of the p38 MAPK pathway in the genesis and progression of malignant brain tumors.

Keywords: brain tumors; glioma; mitogen-activated protein kinases; p38 MAPK inhibitors; small molecules.

Publication types

Review