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Himanshu Mishra Highlights The Role of Pyk2 Kinase in Glioblastoma Progression and Therapeutic Targeting

Collage photo of Lilia Kucheryavykh and Yuriy Kucheryavykh

Aug 11, 2025, 19:13

Himanshu Mishra Highlights The Role of Pyk2 Kinase in Glioblastoma Progression and Therapeutic Targeting

Himanshu Mishra, Microbiologist At Zydus Lifescience pvt Ltd Ahemdabad, shared a post on LinkedIn:

“The Role of Pyk2 Kinase in Glioblastoma Progression and Therapeutic Targeting:-

•Pyk2 is a non‑receptor tyrosine kinase (FAK family) that promotes glioma cell migration, invasion, and therapy resistance. Preclinical work shows knocking down or pharmacologically inhibiting Pyk2 reduces GBM motility and slows growth, and combining Pyk2/FAK inhibitors with temozolomide (TMZ) can be synergistic in mouse models. However, single‑agent FAK/Pyk2 inhibitors have shown only modest benefit clinically so far; the most promising paths are combination therapies, brain‑penetrant dual FAK/Pyk2 inhibitors or degraders, and biomarker‑driven patient selection.

Mechanism:- Pyk2 activation in glioma cells increases motility and invasion, and may be linked to tumor regrowth. It associates with integrin/ECM signalling and localizes at focal adhesions. Pyk2 is implicated in tumor cell behavior and microenvironment interactions.

Preclincal Therapeutic Evidence:- Genetic knockdown and microRNAs decrease GBM migration and invasion, while small-molecule inhibitors, when paired with TMZ, improve outcomes in mouse glioma models and reduce migration.

Clinical Trial and Challenges:- Clinical trials are underway for FAK/Pyk2 inhibitors, with some trials in GBM. However, single agents have minimal clinical benefits. Challenges include toxicity, compensatory signaling networks, functional redundancy, blood-brain barrier penetration, and lack of predictive biomarkers.

Practical Therapeutics strategies under Consideration:- Dual FAK/Pyk2 inhibitors penetrate the brain, combining radiation and temozolomide for preclinical synergy. Highly selective Pyk2 inhibitors address scaffolding roles, reducing off-target toxicity. Biomarker stratification helps select patients for benefit.”

Title: The Role of Pyk2 Kinase in Glioblastoma Progression and Therapeutic Targeting

Authors: Lilia Kucheryavykh,Yuriy Kucheryavykh

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Himanshu Mishra