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Treating Triple Negative Breast Cancer (TNBC) by Blocking RGFR and Fak Kinases

Technology Number: 

1821
Summary 

A novel method for treating triple negative breast cancer (TNBC) by combined inhibition of epidermal growth factor receptor (EGFR) and members of the Fak family, more specifically Proline-rich tyrosine kinase 2 (PYK2) or focal adhesion kinase (FAK).

TNBC is a highly aggressive form of breast cancer, which is characterized by absence of the estrogen and progesterone receptors and lack of HER2 amplification. TNBC is associated with poor prognosis and has no effective targeted treatment. EGFR is highly expressed in ~50% of TNBC patients, and though it is considered a therapeutic target, targeting EGFR alone does not improve the clinical outcome of TNBC. As there is likely compensatory signaling by other molecules that bypass EGFR inhibition.

The group of Prof. Sima Lev has found a method to inhibit EGFR as well as two members of the Fak family kinases, namely PYK2 and FAK. By using extensive in vitro and in vivo work, the group managed to show that combined inhibition of EGFR and FAK/PYK2 obstructs TNBC growth.

Applications


  •   Treating TNBC with elevated EGFR levels.

  •   Ex vivo diagnosis of TNBC severity by measuring levels of tyrosine kinase receptors (e.g. EGFR) and Fak family members.

  •   Combined inhibition of kinases leads to a novel mechanism with beneficial synergistic effects.


Advantages


 


Technology's Essence


Prof. Lev's research group discovered that targeting FAK/PYK2 in different triple negative breast cancer (TNBC) cell lines reduced cellular growth. Therefore, they examined the effect of targeting FAK/PYK2 by shRNA or commercially available inhibitors as well as inhibiting EGFR by small molecules that are used to treat EGFR-related cancers. In vitro essays showed that combined inhibition of EGFR and FAK/PYK2 significantly reduced proliferation of TNBC basal-like cell lines, compared to EGFR inhibition alone. The group next tested the effect of PYK2 knock-down and EGFR inhibition by the drug gefitinib in vivo in a xenograted mouse model, which led to a significant reduction of tumor size by 30-40%.

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