Targeting guanine nucleotide exchange factors for novel cancer drug discovery.

Autor:	Bannoura SF; Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA., Khan HY; Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA., Uddin MH; Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA., Mohammad RM; Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA., Pasche BC; Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA., Azmi AS; Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
Jazyk:	angličtina
Zdroj:	Expert opinion on drug discovery [Expert Opin Drug Discov] 2024 Aug; Vol. 19 (8), pp. 949-959. Date of Electronic Publication: 2024 Jun 17.
DOI:	10.1080/17460441.2024.2368242
Abstrakt:	Introduction: Guanine nucleotide exchange factors (GEFs) regulate the activation of small GTPases (G proteins) of the Ras superfamily proteins controlling cellular functions. Ras superfamily proteins act as 'molecular switches' that are turned 'ON' by guanine exchange. There are five major groups of Ras family GTPases: Ras, Ran, Rho, Rab and Arf, with a variety of different GEFs regulating their GTP loading. GEFs have been implicated in various diseases including cancer. This makes GEFs attractive targets to modulate signaling networks controlled by small GTPases. Areas Covered: In this review, the roles and mechanisms of GEFs in malignancy are outlined. The mechanism of guanine exchange activity by GEFs on a small GTPase is illustrated. Then, some examples of GEFs that are significant in cancer are presented with a discussion on recent progress in therapeutic targeting efforts using a variety of approaches. Expert Opinion: Recently, GEFs have emerged as potential therapeutic targets for novel cancer drug development. Targeting small GTPases is challenging; thus, targeting their activation by GEFs is a promising strategy. Most GEF-targeted drugs are still in preclinical development. A deeper biological understanding of the underlying mechanisms of GEF activity and utilizing advanced technology are necessary to enhance drug discovery for GEFs in cancer.
Databáze:	MEDLINE
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