In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 13_Supplement ( 2020-07-01), p. B70-B70
Kurzfassung:
Rac1 is a high-value therapeutic target for cancer based on its tumor-promoting activities, yet clinical applications targeting Rac1 are in their infancy. High expression and hyperactivation of Rac1 in ovarian cancer, along with our identification of R-ketorolac as a novel Rac1 and Cdc42 selective inhibitor with translational potential, prompt us to test the hypothesis that targeting Rac1 has therapeutic utility for ovarian cancer. Ascites tumor cell samples from ovarian cancer patients in a prospective study receiving racemic ketorolac for clinically indicated use in pain relief were previously reported to show time-dependent reduction of Rac1 and Cdc42 activities post-treatment. New RNA seq data of these patient samples reveals significant downregulation of genes involved in endocytosis, regulation of actin cytoskeleton, ER protein processing, TNF and NOD signaling. Conversely, the identified downregulated genes were overexpressed and associated with worse survival in ovarian cancer patients analyzed through The Cancer Genome Atlas (TCGA). Among the downregulated genes in the NOD pathway are chemokines and proinflammatory cytokines. Follow-up cytokine panels from patients confirm that racemic ketorolac treatment reduces the levels of immunosuppressive cytokines IL-6, IL-10, and RANTES in ascites fluids. Together, these data indicate there may be a benefit to the anti-inflammatory activity of the S- enantiomer, as well as the GTPase inhibitory activity of the R-enantiomer of ketorolac for ovarian cancer treatment. Citation Format: Melanie Rivera, Martha M. Grimes, Dayna Dominguez, S. Ray Kenney, Yuna Guo, Elsa Romero, Kathryn J. Brayer, Yan Guo, Scott A. Ness, Sarah F. Adams, Carolyn Muller, Laurie G. Hudson, Angela Wandinger-Ness. Rac1 as a therapeutic target in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B70.
Materialart:
Online-Ressource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1557-3265.OVCA19-B70
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2020
ZDB Id:
1225457-5
ZDB Id:
2036787-9
