FAK Inhibitor / PTK2 Inhibitor (BI 853520)

Focal adhesion kinase (FAK), also known as protein tyrosine kinase 2 (PTK2), is a major structural and functional component of the focal adhesion complex that is located at the cell membrane and acts as a mechanical adhesion point of the cell to the extracellular matrix and as a signal transducer, integrating signals from growth factors and cell adhesion receptors.1–3

FAK is overexpressed and activated in several forms of advanced-stage solid cancers.4 This can contribute to resistance of anoiksis (cell detachment-induced cell death) and also to increased signalling transduction via the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK) pathways, resulting in an enhanced ability of detached cancer cells to survive and grow.5

Targeted inhibition of FAK/PTK2 kinase activity may therefore confer particular therapeutic benefits in specific types of tumour.2,3,6

Boehringer Ingelheim is investigating BI 853520, a FAK/PTK2 inhibitor, which is currently being investigated in clinical trials in patients with advanced or metastatic solid tumours.7, 8

  1. McLean GW, Carragher NO, Avizienyte E, et al. The role of focal-adhesion kinase in cancer - a new therapeutic opportunity. Nat Rev Cancer 2005;5(7):505–515.
  2. Lim ST, Mikolon D, Stupack DG, Schlaepfer DD. FERM control of FAK function: implications for cancer therapy. Cell Cycle 2008;7(15):2306–2314.
  3. Mitra SK, Schlaepfer DD. Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol 2006;18(5):516–523.
  4. Sulzmaier FJ, Jean C, Schlaepfer DD. FAK in cancer: mechanistic findings and clinical applications. Nat Rev Cancer 2014;14(9):598–610.
  5. Siesser PM, Hanks SK. The signaling and biological implications of FAK overexpression in cancer. Clin Cancer Res 2006;12(11 Pt 1):3233–3237.
  6. Pylayeva Y, Gillen KM, Gerald W, et al. Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling. J Clin Invest 2009;119(2):252–266.
  7. ClinicalTrials.gov. NCT01335269. https://clinicaltrials.gov/ct2/show/study/NCT01335269 (Accessed: August 2016).
  8. ClinicalTrials.gov. NCT01905111. https://clinicaltrials.gov/ct2/show/study/NCT01905111 (Accessed: August 2016).