Targeted therapy proves effective against brain tumors in preclinical studies

FAK is overexpressed, or produced in excessive amounts, in tumor cells, and has been shown to play a key role in survival of cancer cells. In this study, a team led by Vita M. Golubovskaya, PhD, an Associate Professor of Oncology in the Department of Surgical Oncology, found that animal models treated with CFAK-Y15 demonstrated significantly prolonged survival compared to the control group. CFAK-Y15 provides FAK kinase-specific inhibition by upstream targeting of autophosphorylation sites on the FAK protein. It belongs to a class of 'two for one' compounds that also inhibit the oncoprotein Src by inhibiting its autophosphorylation.

"We found that CFAK-Y15 significantly decreased the viability of the glioblastoma cells, and in many cases appeared to cause tumor shrinkage -- especially when CFAK-Y15 was given in combination with temozolomide," noted Dr. Golubovskaya, the paper's first author. "These compounds target FAK signaling, which is critical for cancer cell and cancer stem cell survival, especially in invasive and metastatic cancers."

"We're eager to see this research move to the clinical phase because of the great need for more effective treatments for glioblastoma," noted senior author William G. Cance, MD, FACS, Surgeon-in-Chief and Chair of the Department of Surgical Oncology. "The potential impact is great because glioblastomas are such an aggressive tumor, and because we know they produce FAK in especially high quantities."

The authors also included researchers from the University of California at San Diego and faculty from the Department of Pathology at RPCI. CFAK-Y15 is being developed by CureFAKtor Pharmaceuticals LLC. Drs. Cance and Golubovskaya, both of whom also serve on the management team of CureFAKtor, were part of the team that first identified CFAK-Y15, in research published in the Journal of Medicinal Chemistry in 2008.