Pre-clinical research results presented at the European Society for Medical Oncology (ESMO) 13th World Congress on Gastrointestinal Cancer in Barcelona, Spain shows that novel Focal Adhesion Kinase (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. The research was conducted by scientists of CureFAKtor Pharmaceuticals at the Roswell Park Cancer Institute in Buffalo, New York.
Focal adhesion Kinase (FAK) is substantially over-expressed in many solid tumors. FAK operates by placing itself at the contact points between tumor cells and the extra cellular matrix that surrounds them. Studies have found that in this role, FAK is an important facilitator for signals that cause tumor cells to survive, grow, and produce new blood vessels to sustain growth and travel to distant places within the body where they may establish new tumor sites. It also cocoons the tumor cells to protect them from the body’s natural signaling mechanisms that would cause deviant tumor cells to be eliminated. In a similar fashion, FAK protects tumors from chemotherapeutic drugs and radiation, allowing the tumor cells to resist these therapies.
Research results
In a poster presentation, Elena Kurenova M.D. reported the antiangiogenic effect of a 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.
Blood vessel density
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 (mm). Tumors from both groups demonstrated statistically significant reduction of blood vessels per square mm equaling blood vessel density.
Disrupting signaling
Another 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.
A prolonged effect on pancreatic tumor growth
The study also found that CFAK-C4 combined with gemcitabine (Gemzar?,Eli Lilly & Company) 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.
“We continue to gain knowledge about the activity of our lead compound, CFAK-C4, and this most recent study furthers our understanding of FAK inhibitors and the potential of this compound,” said H. Shep Wild, President and Chief Executive Officer of CureFAKtor Pharmaceuticals. “CureFAKtor’s proprietary FAK technology platform may represent a significant breakthrough in the treatment of most solid tumor cancers in that its unique mechanism of action disrupts the signaling of specific protein to protein binding between FAK and tumors.”
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, a disease with the lowest survival rate of any cancer and limited patient treatment options.
CureFAKtor Pharmaceuticals is a biopharmaceutical company focused on the research and development of Focal Adhesion Kinase therapies to prevent or treat cancer. The Company has identified more than 40 compounds that target specific FAK signaling sites. CureFAKtor’s investigational and combination therapy products target pancreatic, breast, colon, melanoma, lung and brain oncology disorders. CureFAKtor research is conducted at the Roswell Park Cancer Institute. CureFAKtor is planning a Phase I clinical study of CFAK-C4 in combination with gemcitabine chemotherapy, the current standard of care for pancreatic cancer, in 2012.
For more information:
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