Revolutionizing Cancer Treatment with FAK-Based Solutions
At FAKnostics, our research centers around Focal Adhesion Kinase (FAK), a protein that serves as a crucial interface between a cell's interior and exterior. FAK acts as both a sensor and an effector, playing a pivotal role in cancer progression.
are hubs for
cancer cell signal transduction, proliferation, invasion and metastasis.
FAK is a critical tyrosine kinase and scaffolding protein in focal adhesions that is essential for cancer invasion and metastasis!
Traditional methods targeting the kinase domain have been unsuccessful due to rapid kinome reprogramming (15 minutes) and poor selectivity, resulting in low efficacy and high toxicity. Numerous clinical trials have failed because of this.
Focal Adhesion Targeting (FAT) Domain
We target the FAT (Focal Adhesion Targeting ) domain that regulates the Focal Adhesion Complex, metastasis, and apoptosis. Disrupting FAT interactions de-localizes FAK from the critical signaling complex and renders the inhibition strategy much more effective.
Hydrocarbon-stapled peptides that block the FAK FAT domain
Our peptides have demonstrated enhanced alpha helicity, permeability, binding affinity, proteolytic resistance, and pharmacokinetic properties.
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 in cancerous tissue reduces metastasis and increases apoptosis.
FAK overexpression in metastatic tissue
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.
FAK in Fibrosis
Inhibition of FAK reduces fibrosis in a variety of tissues.
Secretion of Extracellular Matrix (ECM) proteins such as collagen and fibronectin
Fibroblast Migration & Proliferation
FAK roles in fibrosis include:
We have currently three pre-clinical programs in the application of our FAK inhibitor to fibrotic diseases. Preliminary data in our targeting of the FAT domain of FAK show superior results in reducing Liver, Lung and Skin Fibrosis relative to the kinase-domain targeting.
This test is based on our proprietary FAK 4.47 antibody that has a very high affinity to FAK.
The ImmunoHistoChemical (IHC) kit/test:
1. Detects FAK positivity in virtually all solid tumors
2. Tested & validated in thousands of human samples
3. Can be utilized for clinical prognosis and patient selection
We believe our findings will improve the NCCN guidelines based on FAK staining.
Our mission is to save lives and we strongly believe that every Stage-1 colorectal cancer patient should be tested with the FAKnosTEST™
We are also using our proprietary antibody in the design of Companion Diagnostics for cancer therapies based on our FAK peptide inhibitor
Marlowe T, Alvarado C, Rivera A, Lenzo F, Nott R, Bondugji D, Montoya J, Hurley A, Kaplan M, Capaldi A, Cance WG. Development of a high-throughput fluorescence polarization assay to detect inhibitors of FAK-Paxillin binding. SLAS Discovery. 2019. Sep 12:2472555219874313. doi: 10.1177/2472555219874313. PMID: 31513463.
Golubovskaya VM, Ylagan L, Miller A, Hughes M, Wilson J, Wang D, Brese E, Bshara W, Edge S, Morrison C, Cance, WG. High focal adhesion kinase expression in breast carcinoma is associated with lymphovascular invasion and triple-negative phenotype. BMC Cancer October 2014; 14(1): 769. PMID: 25326692
O’Brien S, Golubovskaya VM, Conroy J, Liu S, Wang D, Liu B, Cance, WG. FAK inhibition with small molecule inhibitor Y15 decreased viability, clonogenicity, and cell attachment in thyroid cancer cell lines and synergizes with targeted therapeutics. Oncotarget 2014; 5(17): 7945-7959. PMID: 25277205.
Kurenova E, Xu L, Yang X, Baldwin A, Craven R, Hanks S, Liu Z, Cance WG. Focal adhesion kinase suppresses apoptosis by binding to the death domain of receptor interacting protein. Mol Cell Biol 2004; 24(10):4361-4371. PMID: 15121855
First to demonstrate FAK suppresses apoptosis in tumor cells by binding death receptors
Golubovskaya V, Kaur A, Cance WG. Cloning and characterization of the promoter region of human focal adhesion kinase gene: nuclear factor kappa B and p53 binding sites. Biochim Biophys Acta 2004; 25;1678(2-3):111-125. PMID: 15157737
First to clone the promoter of the FAK gene and demonstrate potential regulation by NFkB and p53
Golubovskaya VM, Gross S, Kaur AS, Wilson RJ, Xu LH, Yang XH, Cance WG. Simultaneous inhibition of focal adhesion kinase and Src enhances detachment and apoptosis in colon cancer cell lines. Mol Cancer Res 2003; 1(10):755-764. PMID: 12939401
Demonstration of synergy between FAK inhibition and Src inhibition in colon cancer cells
Lik Hang Lee, Lindy Davis, Lourdes Ylagan, Angela R Omilian, Kristopher Attwood,
Canan Firat, Jinru Shia, Philip B Paty, William G Cance. Identification of a Subset of Stage Journal of the National Cancer Institute
Golubovskaya V, Beviglia L, Xu L-H, Earp HS, Craven R, Cance WG. Dual inhibition of focal adhesion kinase and epidermal growth factor receptor pathways cooperatively induces death receptor-mediated apoptosis in human breast cancer cells. J Biol Chem 2002; 277(41):38978-38987. PMID: 12167618
Demonstration of synergy between FAK inhibition and epidermal growth factor (EGFR) inhibition in human breast cancer cells
Xu L-H, Yang X, Bradham CA, Brenner DA, Baldwin AS, Craven RJ, Cance WG. The focal adhesion kinase suppresses transformation-associated anchorage-independent apoptosis in human breast cancer cells: Involvement of death receptor-related signaling pathways. J Biol Chem 2000; 275(39):30597-30604. PMID: 10899173
First proof of principle for targeting the FAT domain with adenoviral-mediated gene delivery, linking FAK to death receptor-related signaling pathways in tumor cells
Xu L-H, Yang X, Craven RJ, Cance WG. The COOH-terminal domain of the focal adhesion kinase induces loss of adhesion and cell death in human tumor cells. Cell Growth Differ 1998; 9(12):999-1005. PMID: 9869300
Targeting the C-terminal domain of FAK (the Focal Adhesion targeting domain) was a therapeutic strategy in human tumors
Xu L-H, Owens LV, Sturge GC, Yang X, Liu ET, Craven RJ, Cance WG. Attenuation of the expression of the focal adhesion kinase induces apoptosis in tumor cells. Cell Growth Differ 1996; 7(4):413-418. PMID: 9052982
First demonstration linking FAK attenuation to apoptosis (programmed cell death) in tumor cells