Targeting guanine nucleotide exchange factors for novel cancer drug discovery.
Expert Opin Drug Discov
; 19(8): 949-959, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38884380
ABSTRACT
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Guanine Nucleotide Exchange Factors
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Drug Discovery
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Molecular Targeted Therapy
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Drug Development
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Neoplasms
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Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
Expert Opin Drug Discov
Year:
2024
Type:
Article
Affiliation country:
United States