Abstract 1923: Identification and validation of Integrin-Linked Kinase (ILK) signaling as a therapeutic target for ovarian cancer

Abstract

Abstract Ovarian cancer affects approximately 25,000 women and contributes to around 14,000 deaths in the United States each year. Although significant advances have been made in the discovery of molecular diagnostics and therapeutics for other cancers, ovarian cancer still lacks reliable diagnostic and prognostic markers as well as appropriate targeted therapeutics. A major reason for the lagging development of targeted therapeutics is the molecular heterogeneity of high grade serous ovarian cancer and the lack of better understanding of driver mutations and pathogenesis. Although gene expression data sets are available, most of them lack appropriate pair-matched controls to define the alterations that result in the transformation of normal ovarian cells to highly proliferative cancerous cells. We compared differential gene expression of high-grade treatment-naïve ovarian cancer tissue samples to matched-pair adjacent benign ovarian tissue specimens from 24 patients. A significant upregulation of the integrin-linked kinase (ILK) pathway was identified in 22 of the 24 cancer specimens, identifying a potential player that could contribute to the transformation of normal ovarian cells to cancerous cells. To determine the therapeutic potential of ILK inhibition, ILK expression was reduced using siRNA in SKOV3 cells, which resulted in decreased cell proliferation. This is consistent with prior studies demonstrating reduced adhesion to and invasion of collagen gels and organotypic meso-mimetic ovarian cancer cultures with down-regulating ILK using siRNA resulted in. We then assessed the ability of a targeted agent, compound 22, a small molecule ILK-selective inhibitor, to inhibit proliferation in various ovarian cancer cell lines with different phenotypic characteristics (SKOV3, OVCAR3, OVCAR8, OV90). Compound 22 reduced the phosphorylation of Akt, a downstream target of ILK, and also inhibited cellular proliferation. Our initial findings validate ILK as a potential therapeutic target for molecular inhibition in ovarian cancer and warrants further investigation. Citation Format: Michael A. Ulm, Suriyan Ponnusamy, Adam C. ElNaggar, Ramesh Narayanan. Identification and validation of Integrin-Linked Kinase (ILK) signaling as a therapeutic target for ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1923.