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OUR

HISTORY

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OUR TEAM AT FAKNOSTICS HAS BEEN AT THE FOREFRONT OF FAK RESEARCH AND DEVELOPMENT SINCE 1991

2022 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 I Colorectal Cancer Patients with High Recurrence Risk. Journal of the National Cancer Institute, djac023, https://doi.org/10.1093/jnci/djac023

 

2021 Initiation of the cooperation with the Institute for Digital Medicine at the Augsburg University Clinic to digitize FAKnosTest for high throughput automated pathology. 

2021-PRESENT - OPTIMIZATION OF FAKnosTEST™

2020-PRESENT - COMMERCIALIZATION OF FAKNOSTICS™

2020 Formation of FAKnostics Biologics LLC, our affiliated entity focused on the production of the proprietary 4.47 antibody, that is the principal functional reagent for our pathology test.

2014-PRESENT Structural-based approaches to development of novel FAK inhibitors

2016 Demonstration of the pitfalls of FAK kinase inhibition as a therapeutic, with the rapid development of resistance to kinase-targeted inhibition

2009-2015 Proof-of-principle studies of small molecule FAK inhibitors targeting the FAK scaffold

2020 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.

2019 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

2019 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.

2019 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.

2016 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

2013 Reviewed in: 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

2004-2009 Demonstrated multiple ways FAK promotes tumor cell survival and metastasis through binding and inhibition of natural growth-regulatory protein (i.e., p53)

2009 First demonstration that neurofibromin binds to FAK

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

2008 First demonstration that p53 regulates FAK expression in human tumor cells

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

Key review paper: Cance WG and Golubovskaya VM.  Focal Adhesion Kinase (FAK) versus p53: apoptosis or survival? Sci Signal 2008; 1(20):pe22.  PMID:  18493017

2005 First to demonstrate that FAK binds to p53 to suppress apoptosis

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

2004 First to clone the promoter of the FAK gene and demonstrate potential regulation by NFkB and p53

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

2004 First to demonstrate FAK suppresses apoptosis in tumor cells by binding death receptors

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

2002-2004 Demonstration of therapeutic synergy targeting FAK and other tyrosine kinases (i.e., EGFR)

2003 Demonstration of synergy between FAK inhibition and Src inhibition in colon cancer cells

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

2002 Demonstration of synergy between FAK inhibition and epidermal growth factor (EGFR) inhibition in human breast cancer cells

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

1991-2002 Development of novel approaches to target FAK through disruption of its localization in tumor cells (i.e., antisense, adenoviral gene therapy).

2000 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, 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

2000 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, 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

1998 Targeting the C-terminal domain of FAK (the Focal Adhesion targeting domain) was a therapeutic strategy in human tumors

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

1996 First demonstration linking FAK attenuation to apoptosis (programmed cell death) in tumor cells

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

1993 First demonstration of elevated levels of FAK in invasive human tumors

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