Abstract C29: FAK inhibition targets cancer stem cells

Targeting cancer stem cells (CSCs) holds promise to address key challenges of cancer treatment: chemo- and radiation therapy resistance, metastasis, and recurrence. Increased CSC abundance after neoadjuvant chemotherapy has been associated with a significantly worse outcome. Combining CSC-targeted agents with chemotherapy may lead to more durable response with increased overall survival.Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, mediates signal transduction by integrins and growth factor receptors to regulate cellular adhesion, proliferation, migration, and survival. Several studies have demonstrated that FAK expression and kinase activity are necessary for survival and maintenance of CSCs. FAK is also upregulated in many epithelial tumors and associated with poor patient prognosis and therefore has been pursued as a promising therapeutic target for cancer. VS-6063 and VS-4718 are orally bioavailable small molecules that impede CSCs through the inhibition of FAK. Both VS-6063 and VS-4718 preferentially kill CSCs in multiple cancer models, including models of breast, ovarian, SCLC, and mesothelioma, and these agents are in clinical development. We demonstrate that treatment of cancer cell lines or mice bearing xenograft tumors with VS-6063 or VS-4718 decreases CSCs as assessed by decreased tumor-initiating capability in limiting dilution assays. Both FAK inhibitors decrease significantly CSCs to a varying degrees across multiple tumor models. Furthermore, tre...

Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Kolev, V., Wang, Y., Sprott, K., Shapiro, I., Ring, J., Pachter, J., Weaver, D. Tags: Cancer Stem Cells: Poster Presentations - Proffered Abstracts Source Type: research