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Kinase Inhibitor Decreases Pancreatic Cancer Tumor Blood Flow

By Drug Discovery Trends Editor | June 23, 2011

CureFAKtor Pharmaceuticals presented preclinical research results demonstrating that FAK inhibitors targeting the binding site of vascular endothelial growth factor receptor 3 (VEGFR-3) decrease pancreatic cancer tumor blood flow and reduce blood vessel density in vivo. 

CureFAKtor senior scientist Elena Kurenova, MD, reported the anti-angiogenic effect of the company’s small molecule compound, CFAK-C4, in pancreatic cancer tumors.  Contrast-enhanced magnetic resonance imaging (MRI) revealed significant reduction in tumor vascular volume and permeability in CFAK-C4-treated pancreatic tumors in vivo.  MRI-based changes in tumor vascularity were seen at both the first and second week after therapy.

CureFAKtor scientists analyzed the blood vessel density in a subcutaneous mouse pancreatic tumor model in two CFAK-C4 treated groups and compared vessel density to control group tumors treated with phosphate-buffered saline (PBS). One group was treated for 35 days with treatment starting the day after cell injection.  The second treatment group started when tumors reached a volume of 100 cubic millimeters. Tumors from both groups demonstrated statistically significant reduction of blood vessels per square mm equaling blood vessel density.

A CureFAKtor study reported earlier this year pinpointed the site of interaction of VEGFR-3 and FAK to create small molecule drugs capable of disrupting signaling and causing death of pancreatic cancer cells.  CFAK-C4, reduced tumor growth in vivo in mouse pancreatic cancer cells by up to 60%, and CFAK-C4 combined with chemotherapy drug gemcitabine had a synergistic effect and led to 80% pancreatic cancer tumor reduction. 

The study also found that CFAK-C4 combined with gemcitabine had a prolonged effect on pancreatic tumor growth.  Two weeks after treatment, the tumor size in the previously treated group was approximately 75% smaller than the tumor in the control group. The researchers concluded that targeting FAK with small molecule inhibitors can be effectively used to develop potential oral-based cancer therapies.

Earlier this year, CureFAKtor received orphan drug designation by the U.S. Food and Drug Administration (FDA) for CFAK-C4 in combination with gemcitabine for the treatment of pancreatic cancer.

Release Date: June 23, 2011 
Source: CureFAKtor Pharmaceuticals 


Filed Under: Drug Discovery

 

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