The FAK inhibitor BI 853520 exerts anti-tumor effects in breast cancer

Abstract

Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that regulates a plethora of downstream signaling pathways essential for cell migration, proliferation and death, processes that are exploited by cancer cells during malignant progression. These well-established tumorigenic activities, together with its high expression and activity in different cancer types, highlight FAK as an attractive target for cancer therapy. We have assessed and characterized the therapeutic potential and the biological effects of BI 853520, a novel small chemical inhibitor of FAK, in several preclinical mouse models of breast cancer. Treatment with BI 853520 elicits a significant reduction in primary tumor growth caused by an anti-proliferative activity by BI 853520. In contrast, BI 853520 exerts effects with varying degrees of robustness on the different stages of the metastatic cascade. Together, the data demonstrate that the repression of FAK activity by the specific FAK inhibitor BI 853520 offers a promising anti-proliferative approach for cancer therapy.

The roles of nuclear focal adhesion kinase (FAK) on Cancer: a focused review

“…And reported FAK inhibitors are mainly small molecule inhibitors [1]. Small chemical molecules with good drug-forming properties can inhibit the phosphorylation of FAK and block the signal transduction through the cell membrane, thereby inhibiting the proliferation and spread of cancer cells [117]. Therefore, the research on FAK inhibitors is very promising.…”

Molecular Complexity of Lymphovascular Invasion: The Role of Cell Migration in Breast Cancer as a Prototype

“…Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that is associated with a plethora of singling pathways fundamental to cell cancer migration, proliferation, death and tumour survival [110]. According to Golubovskaya et al [111], high FAK levels correlated strongly with aggressive BC subtypes such as TN BC as well as with LVI, hence FAK might be a target for therapeutic intervention in these patients.…”

Highly Selective PTK2 Proteolysis Targeting Chimeras to Probe Focal Adhesion Kinase Scaffolding Functions

“…We previously described BI-853520, a novel ATP-competitive inhibitor distinguished by high potency and selectivity 15,16 . BI-853520 inhibits PTK2 autophosphorylation in cancer cell lines and blocks anchorage-independent proliferation with single digit nmol/L potency.…”