Focal Adhesion Kinase (FAK), a member of a family of nonreceptor protein-tyrosine kinases, is substantially over-expressed in many cancers, including breast, thyroid, prostate, colon, cervical, ovarian, liver and pancreatic cancer [1, 2]. FAK operates by placing itself at the contact points between tumor cells and the extra cellular matrix that surrounds them.
Researchers have found that 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 and survive these therapies.
FAK inhibitors offer therapeutic potential
The importance of FAK as a regulator of normal cellular function was first underscored when researchers observed that a number of cancers had alterations in FAK expression and/or activity. Because increased FAK expression and activity are now recognized as hallmarks of many cancers and the observations that increased cell migration often characterizes tumor cells with increased metastatic potential, FAK inhibitors may have therapeutic potential for the treatment of cancer.
Orphan Drug Status
CFAK-C4, which is in development for the treatment of pancreatic cancer by CureFAKtor Pharmaceuticals, LLC, a privately-held biopharmaceutical company focused on the research and development of Focal Adhesion Kinase (FAK) inhibitors for cancer, has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA).
The orphan status is given to drugs and biologics that are being developed to treat rare medical conditions, specifically those affecting fewer than 200,000 persons in the U.S. The designation provides for a number of potential incentives related to CFAK-C4, including a seven-year period of marketing exclusivity, reduced regulatory fees, certain tax credits, and additional regulatory support for research and development initiatives.
"Receiving Orphan Drug Designation by the FDA is an important milestone for CureFAKtor, as well as for pancreatic cancer patients who have the lowest survival rate of any cancer and limited treatment options," said H. Shep Wild, President and Chief Executive Officer of CureFAKtor Pharmaceuticals. "CFAK-C4 is the first clinical candidate derived from our broad FAK technology platform and we look forward to progressing CFAK-C4 into human clinical trials."
A Phase I clinical study of CFAK-C4 in combination with gemcitabine chemotherapy, the current standard of care for pancreatic cancer, is planned to start in 2012.
CureFAKtor Pharmaceuticals the developer of CFAK-C4, formed in 2008 based on fundamental discoveries, has been funded primarily by grants from the National Institutes of Health (NIH). The company’s proprietary FAK technology platform may represent a significant breakthrough in the treatment of most solid tumors in that its unique mechanism of action disrupts the signaling of FAK in tumors by targeting specific protein to protein bindings. Since FAK is over-expressed in virtually all solid tumors, the technology has broad applicability in oncology.
"Focal Adhesion Kinase protein binding inhibitors represent a promising area of research as FAK is expressed at extremely high levels in solid cancer tumors to serve as a survival mechanism by signaling tumor growth, invasion and metastasis.
“Groundbreaking work by Dr. William Cance, Chair, Surgical Oncology, Surgeon-in-Chief Roswell Park Cancer Institute, has shown that FAK protects tumors from chemotherapy, radiation and the body's natural defenses," said Dr. H. Shelton Earp III, M.D., Professor and Director of Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill School of Medicine. "While still early stage, I look forward to further research into the effect CFAK-C4 may have on solid tumors."
 Gabarra-Niecko, V., Schaller, M. D., Dunty, J. M. (2003) Cancer Metastasis Rev. 22, 359–374
 McLean, G. W., Carragher, N. O., Avizienyte, E., Evans, J., Brunton, V. G., and Frame, M. C. (2005) Nat. Rev. Cancer 5, 505–515
 Jill K. Slack-Davis JK, Martin KM, Tilghman RW, et al Cellular Characterization of a Novel Focal Adhesion Kinase Inhibitor. J Bio Chem. 2007, 282, 20, 14845–52,