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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.

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Focal adhesions

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

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Kinase Domain

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.

Our Solution

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

Normal

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Metastatic Cancer

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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

  • Myofibroblast Differentiation

  • 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.

FAK-based Diagnostics

FAKnosTEST™

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
Doctor and Patient

News

FAKnostics R&D Updates

Publications

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Stahl E, Koessel K, Weiner W, Miller J, Cance WG, Marlowe T. Computational-based discovery of novel FAK FERM domain chemical probes that block HER2-FAK cancer signaling. Chem. Biol. Drug Des. 2020. PMID: 32080977.

Alvarado C, Stahl E, Koessel K, Rivera A, Cherry B, Pulavarti SV, Szyperski T, Cance WG, Marlowe T.Development of a fragment-based screening assay for the focal adhesion targeting domain using SPR and NMR.Molecules. 2019. 24(18), 3352. PMID: 31540099.

Marlowe T, Dementiev A, Figel S, Rivera A, Flavin M, Cance W. High resolution crystal structure of the FAK FERM domain reveals new insights on the druggability of tyrosine 397 and the src SH3 binding site. BMC Mol Cell Biol 2019; 20:10 PMID: 31109284

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.

Marlowe TA, Lenzo FL, Figel SA, Grapes AT, Cance WG. Oncogenic Receptor Tyrosine Kinases Directly Phosphorylate Focal Adhesion Kinase (FAK) as a Resistance Mechanism to FAK-kinase Inhibitors. Mol Cancer Ther. 2016: 15(12): 3028-3039.  PMID:  27638858

Lung Cancer

Zhang H, Shao H, Golubovskaya V, Chen H, Cance WG, Adjei A, Dy G. Efficacy of focal adhesion kinase (FAK) inhibition in non-small cell lung cancer with oncogenically-activated MAPK pathways. Br J Cancer. 2016; 115(2): 203-11. PMID: 2733608.

Melanoma

Kurenova E, Ucar D, Liao J, Yemma M, Gogate P, Bshara W, Sunar U, Seshadri M, Hochwald S, Cance WG. A FAK scaffold inhibitor disrupts FAK and VEGFR-3 signaling and blocks melanoma growth by targeting both tumor and endothelial cells. Cell Cycle 2014; 13 (16): 2542-2553. PMID: 25486195

Breast Cancer

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

Thyroid Cancer

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.

Pancreatic Cancer

Gogate P, Kurenova E, Ethirajan M, Liao J, Yemma M, Sen A, Pandey R, Cance WG. Targeting the C-terminal focal adhesion kinase scaffold in pancreatic cancer. Cancer Lett Jul 2014. [E-pub ahead of print]. PMID: 25067788

Lung Cancer

Dy G, Golubovskaya V, Ylagan L, Pokharel S, Bshara W, Brese E, Morrison C, Cance WG, Miller A. The prognostic significance of focal adhesion kinase (FAK) expression in stage I non-small cell lung cancer. J Thorac Oncol 2014:9:1278-1284. PMID: 25122425

Pancreatic Cancer

Kurenova E, Liao J, He DH, Hunt D, Yemma M, Bshara W, Seshadri M, Cance WG. The FAK scaffold inhibitor C4 disrupts FAK-VEGFR-3 signaling and inhibits pancreatic cancer growth. Oncotarget 2013; 4 (10): 1632-1646. PMID: 24142503

Neuroblastoma

Stewart JE, Ma X, Megison M, Nabers H, Cance WG, Kurenova EV, Beirele EA. Inhibition of FAK and VEGFR-3 binding decreases tumorigenicity in neuroblastoma. Mol Carcinog. 2013 July 19. [Epub ahead of print]. PMID: 23868727

Colorectal Cancer

Heffler M, Golubovskaya VM, Bullard Dunn K, Cance W.  Focal adhesion kinase autophosphorylation inhibition decreases colon cancer cell growth and enhances the efficacy of chemotherapy.  Cancer Biol Ther  2013; 14(8): 761- 772.  PMID: 23792569

Glioblastoma

Golubovskaya V, Huang G, Baotran H, Yemma M, Morrison C, Lee J, Eliceiri B, Cance WG. Pharmacological blockade of FAK autophosphorylation decreases human glioblastoma tumor growth and synergizes with temozolomide. Mol Cancer Ther 2013; 12(2): 162 - 172. PMID: 23243059

Cance WG, Kurenova E, Marlowe T, Golubovskaya V.  FAK as a cancer target:  Disrupting the scaffold to improve focal adhesion kinase-targeted cancer therapeutics.  Sci Signal. 2013 Mar 26; 6(268): pe10.doi: 10.1126/scisignal.2004021.  PMID:  23532331

Melanoma

Ucar DA, Kurenova E, Garrett TJ, Cance WG, Nyberg C, Cox A, Massoli N, Ostrov DA, Lawrence N, Sebti SM, Zajac-Kaye M, Hochwald SN.  Disruption of the protein interaction between FAK and IGF-1R inhibits melanoma tumor growth.  Cell Cycle 2012; 11(17): 3250-3259.  PMID:  22894899

Neuroblastoma

Beierle EA, Trujillo A, Kurenova EV, Cance WG, Golubovskaya VM. Inhibition of focal adhesion kinase and src increases detachment and apoptosis in human neuroblastoma cell lines. Mol Carcinog 2010; 49(3):224-234. PMID: 19885861

Pancreatic Cancer

Zheng D, Golubovskaya V, Kurenova E, Wood C, Massoll NA, Ostrov D, Cance WG, Hochwald SN. A novel strategy to inhibit FAK and IGF-1R decreases growth of pancreatic cancer xenografts. Mol Carcinog 2010; 49(2):200-209. PMID: 19885860

Neuroblastoma

Beierle EA, Ma X, Stewart J, Nyberg C, Trujillo A, Cance WG, Golubovskaya VM. Inhibition of focal adhesion kinase decreases tumor growth in human neuroblastoma. Cell Cycle 2010; 9(5)1005-1015. PMID: 20160475

Breast Cancer

Golubovskaya VM, Zheng M, Zhang L, Li J-L, Cance WG. The direct effect of focal adhesion kinase (FAK), dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis. BMC Cancer 2009; 12(9):280. PMID: 19671193

Pancreatic Cancer

Hochwald SN, Nyberg C, Zheng M, Zheng D, Wood C, Massoll NA, Magis A, Ostrov D, Cance WG, Golubovskaya V. A novel small molecule inhibitor of FAK decreases growth of human pancreatic cancer. Cell Cycle 2009; 8(15):2435-2443. PMID: 19571674

Kweh F, Zheng M, Kurenova E, Wallace M, Golubovskaya V, Cance WG. Neurofibromin physically interacts with the N-terminal domain of focal adhesion kinase. Mol Carcinog 2009; 48(11): 1005-1017. PMID: 19479903

First demonstration that neurofibromin binds to FAK

Neuroblastoma

Beierle EA, Massoll NA, Hartwich J, Kurenova EV, Golubovskaya VM, Cance WG, McGrady P, London WB.: Focal adhesion kinase expression in human neuroblastoma: Immunohistochemical and real-time PCR analyses. Clin Cancer Res 2008; 14(11):3299-3305. PMID: 18519756

Neuroblastoma

Beierle EA, Trujillo A, Nagaram A, Golubovskaya VM, Cance WG, Kurenova EV. TAE226 inhibits human neuroblastoma cell survival. Cancer Invest 2008; 26(2):145-151. PMID: 18259944

Golubovskaya V, Finch R, Virnig C, Kweh F, Massoll N, Campbell-Thompson M, Wallace MR, Cance WG. p53 regulates FAK expression in human tumor cells. Mol Carcinog 2008; 47(5):373-382.  PMID:17999388

First demonstration that p53 regulates FAK expression in human tumor cells

Pancreatic Cancer

Liu W, Bloom DA, Cance WG, Kurenova EV, Golubovskaya VM, Hochwald SN. FAK and IGF-IR interact to provide survival signals in human pancreatic adenocarcinoma cells. Carcinogenesis 2008; 29(6)1096-1107.PMID: 18263593

Breast Cancer

Lark AL, Livasy CA, Dressler L, Moore DT, Millikan RC, Geradts J, Iacocca M, Cowan D, Little D, Craven RJ, Cance WG.  High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype.  Mod Pathol 2005; 18:1289-1294. PMID: 15861214

Melanoma

Smith CS, Golubovskaya VM, Peck E, Xu L-H, Monia BP, Yang, X, Cance WG. Effect of focal adhesion kinase (FAK) downregulation with FAK antisense oligonucleotides and 5-fluorouracil on the viability of melanoma cell lines. Melanoma Res 2005; 15(5):357-362. PMID: 16179862

Golubovskaya VM, Finch R, Cance WG. Direct interaction of the N-terminal domain of focal adhesion kinase with the N-terminal transactivation domain of p53. J Biol Chem 2005; 280(26):25008-25021. PMID: 15855171

First to demonstrate that FAK binds to p53 to suppress apoptosis

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

Colorectal Cancer

Lark AL, Livasy C, Calvo B, Caskey L, Moore DT, Yang X-H, Cance WG. Overexpression of focal adhesion kinase (FAK) in primary colorectal carcinomas and colorectal liver metastases: Immunohistochemistry and real-time PCR analyses. Clin Cancer Res 2003; 9(1):215-222. PMID: 12538472

Colorectal Cancer

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

https://doi.org/10.1093/jnci/djac023

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

Ovarian Cancer

Judson PL, He X, Cance WG, Van Le L. Over-expression of focal adhesion kinase a protein tyrosine kinase in ovarian carcinoma. Cancer 1999; 86(8):1551-1556. PMID: 10526262

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

Thyroid Cancer

Owens LV, Xu L-H, Dent GA, Yang X-H, Sturge GC, Craven RJ, Cance WG. Focal adhesion kinase as a marker of invasive potential in differentiated human thyroid cancer. Ann Surg Oncol 1996; 3(1):100-105. PMID: 8770310

Sarcoma

Owens LV, Weiner, T Xu L, Cance WG. Antisense to the focal adhesion kinase gene disrupts human sarcoma growth and adhesion. Surg Forum 1994; 45:501-503.

Weiner TM, Liu ET, Craven RJ, Cance WG. Expression of focal adhesion kinase (FAK) gene and invasive cancer. Lancet 1993; 342(8878):1024-1025. PMID: 7796399

First demonstration of elevated levels of FAK in invasive human tumors

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