WE ARE DEVELOPING A NOVEL, PEPTIDE-BASED INHIBITOR OF FAK, AS WELL AS A COMPANION DIAGNOSTIC AND PROGNOSTIC TEST
FOCAL ADHESION KINASE
FAK, Focal Adhesion Kinase, (aka Protein Tyrosine Kinase 2, PTK2) is one of the most fascinating and complex proteins in a cell. It serves as an interface between the cell's interior and exterior and has functions of being a sensor and an actuator. It senses external mechanical stimuli such as tension and pressure, and acts as an actuator of various transduction cascades that effect cell motility, adhesion, and local rigidity.
Focal adhesions tether the cytoskeleton to the extra cellular matrix, where cancer cells invade adjacent tissues. Focal adhesions are hubs for transduction, cell migration, invasion and proliferation in the cancer cell.
FAK IS A CRITICAL TYROSINE KINASE ENZYME IN FOCAL ADHESIONS THAT IS ESSENTIAL FOR CANCER TO INVADE AND METASTISIZE
IMPORTANCE OF FAK IN CANCER
Virtually all solid tumors are dependent on FAK signaling including breast, colon, head and neck, thyroid, ovarian, liver, esophageal, brain, stomach, endometrial, lung, sarcoma, neuroblastoma, pancreatic and is massively overexpressed in human melanoma samples.
Inhibiting FAK expression in cancerous tissues reduces metastatic risk and increases chances of apoptosis.
We target the FAT domain that regulates the Focal Adhesion Complex, Metastasis and Apoptosis. Disrupting FAT interactions (i.e. with Paxilin) de-localizes FAK from the critical signaling complex and renders the inhibition strategy much more effective.
We have demonstrated that Stage 1 colorectal cancers with high FAK expression have a significantly higher probability to progress to metastatic outcomes than those with low FAK expression.
We are developing a novel effective methodology of targeting the FAT domain of FAK that we expect to be much more effective than the traditional kinase domain targeting. Our FAKnosTest® pathology test based on our proprietary FAK antibody has very high sensitivity and enables detecting FAK over-expression in early-stage cancer.
IMPORTANCE OF FAK IN FIBROSIS
FAK plays a central role in the action and reaction of cells to the Extra Cellular Matrix, including collagen excretion and formation of fibrosis.
Over-expression of FAK induces increased fibrosis and inhibition of FAK reduces fibrosis in a variety of tissues.
Fibrosis can be induced via biochemical stress. For example, liver fibrosis can be induced either by infectious diseases (e.g. hepatitis) or by over-consumption of alcohol, and resulting in cirrhosis.
Skin fibrosis can also be induced by the natural healing process of the skin from a physical wound, and resulting in scarring and keloids. Inhibition of FAK locally has shown reduction of scarring during the healing process.
We are in preclinical testing of our FAK inhibitor for the treatment of melanoma, specifically patients with NRAS mutation. FAKnostics has demonstrated that our FAK inhibitor has excellent pharmacokinetics and inhibits in vivo tumor growth.
We are currently testing the effectiveness and dosing of our FAK inhibitors for the reduction of skin fibrosis with a view towards plastic surgery applications.
The FAKnostics platform, based on our best-in-class FAK pathway inhibition methodology and diagnostic antibody technology, has the potential to serve as a prognostic tool and therapeutic program to address the unmet needs of cancer and fibrosis patients.