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Updated: Feb 9, 2026

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Published on: November 11, 2018
Targeting Rac and Cdc42 GTPases in Cancer
María Del Mar Maldonado1, Suranganie Dharmawardhane2
1Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
Abstract:
Rac and Cdc42 are small GTPases that have been linked to multiple human cancers and are implicated in epithelial to mesenchymal transition, cell-cycle progression, migration/invasion, tumor growth, angiogenesis, and oncogenic transformation. With the exception of the P29S driver mutation in melanoma, Rac and Cdc42 are not generally mutated in cancer, but are overexpressed (gene amplification and mRNA upregulation) or hyperactivated. Rac and Cdc42 are hyperactivated via signaling through oncogenic cell surface receptors, such as growth factor receptors, which converge on the guanine nucleotide exchange factors that regulate their GDP/GTP exchange. Hence, targeting Rac and Cdc42 represents a promising strategy for precise cancer therapy, as well as for inhibition of bypass signaling that promotes resistance to cell surface receptor-targeted therapies. Therefore, an understanding of the regulatory mechanisms of these pivotal signaling intermediates is key for the development of effective inhibitors. In this review, we focus on the role of Rac and Cdc42 in cancer and summarize the regulatory mechanisms, inhibitory efficacy, and the anticancer potential of Rac- and Cdc42-targeting agents. Cancer Res; 78(12); 3101-11. ©2018 AACR.
Insights
Rac (Ras-related C3 botulinum toxin substrate) and Cdc42 (cell division control protein 42) are key small GTPases in cancer. Targeting these proteins offers a promising strategy for precise cancer therapy and overcoming treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Rac and Cdc42 are small GTPases frequently dysregulated in human cancers.
- They play critical roles in cancer progression, including epithelial to mesenchymal transition, migration, invasion, and tumor growth.
- While not typically mutated, Rac and Cdc42 are often overexpressed or hyperactivated through oncogenic signaling pathways.
Purpose of the Study:
- To review the role of Rac and Cdc42 in various human cancers.
- To summarize the regulatory mechanisms governing Rac and Cdc42 activity.
- To discuss the anticancer potential and inhibitory efficacy of agents targeting Rac and Cdc42.
Main Methods:
- Literature review focusing on Rac and Cdc42 in cancer.
- Analysis of signaling pathways involving Rac and Cdc42 activation.
- Evaluation of therapeutic strategies targeting Rac and Cdc42.
Main Results:
- Rac and Cdc42 are implicated in multiple hallmarks of cancer.
- Hyperactivation occurs via signaling through oncogenic cell surface receptors and guanine nucleotide exchange factors.
- Targeting Rac and Cdc42 shows promise for precise cancer therapy and overcoming resistance to other treatments.
Conclusions:
- Rac and Cdc42 are pivotal signaling intermediates in cancer development and progression.
- Understanding their regulatory mechanisms is crucial for developing effective inhibitors.
- Targeting Rac and Cdc42 represents a viable therapeutic strategy in oncology.
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