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Could FAK and PYK2 Become Therapeutic Targets in CLL? Researchers Say Perhaps

By: Joshua Swore, PhD
Posted: Tuesday, March 14, 2023

The nonreceptor proteins focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2) may prove to be therapeutic targets for patients with chronic lymphocytic leukemia (CLL) and its microenvironment, according to a study published in the Journal of Cellular and Molecular Medicine. Moreover, PYK2 may also serve as a prognostic indicator in this patient population, given its overexpression in CLL, explained Cristina Scielzo, PhD, of IRCCS Ospedale San Raffaele, Milan, and colleagues.

Peripheral blood samples were collected from patients with CLL (n = 36) and healthy donors (n = 10). All samples were cultured and purified. Samples of RNA were extracted and underwent reverse transcription and real-time polymerase chain reaction. Protein expression was determined using Western blot analysis and immunofluorescence.

The study analyses revealed an increased expression of PYK2 in patients with CLL compared with healthy controls, whereas FAK expression demonstrated the opposite trend. The decreased levels of FAK in patients with CLL were associated with more progressive disease. However, this was not observed in patients with decreased PYK2 levels.

Furthermore, the use of the selective ATP-competitive FAK/PYK2 inhibitor defactinib significantly downregulated the activation of both kinases after 4 hours of treatment. Rates of the kinases’ cellular signaling cascade were impaired, demonstrating the potential benefit of defactinib in regulating CLL. However, there was extensive variation in patient response to defactinib treatment, suggesting an increased complexity of the regulatory mechanism.

Disclosure: The study authors reported no conflicts of interest.

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