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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Published on: July 17, 2019

SRC family kinase activity is up-regulated in hormone-refractory prostate cancer

Oleg Tatarov1, Thomas J Mitchell, Morag Seywright

  • 1Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, Glasgow Royal Infirmary, Glasgow, UK.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|May 19, 2009
PubMed
Abstract

Insights

Increased Src family kinase (SFK) activity in prostate cancer patients correlates with shorter survival and metastasis. Targeting SFK with inhibitors like dasatinib shows promise, especially in hormone-refractory AIPC, suggesting patient selection can improve treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Src family kinases (SFKs) are implicated in cancer progression.
  • SFK inhibitors are under investigation for advanced prostate cancer.
  • The relationship between SFK activation and patient survival in AIPC is not well-established.

Purpose of the Study:

  • To investigate if SFK activation increases with progression to androgen-independent prostate cancer (AIPC).
  • To determine if SFK activation correlates with patient survival and metastatic disease.
  • To assess the efficacy of the SFK inhibitor dasatinib in hormone-sensitive and hormone-refractory prostate cancer models.

Main Methods:

  • Immunohistochemistry was used to analyze SFK activity in matched prostate tumor samples from before and after hormone deprivation therapy.
  • Matched hormone-sensitive and hormone-refractory prostate cancer cell lines were treated with dasatinib.
  • Cellular responses including phosphorylation, migration, and proliferation were assessed.

Main Results:

  • A significant increase in SFK activity was observed in 28% of AIPC patients, associated with shorter overall survival (P<0.0001) and distant metastases.
  • Dasatinib effectively inhibited Src, Lyn, and FAK phosphorylation in both hormone-sensitive and hormone-refractory cell lines.
  • Dasatinib reduced cell migration in both models and inhibited proliferation specifically in hormone-refractory cells.

Conclusions:

  • SFK activation is a potential biomarker for aggressive AIPC and poor prognosis.
  • SFK inhibition, particularly with dasatinib, demonstrates therapeutic potential in AIPC, especially in hormone-refractory settings.
  • Patient selection based on SFK activation could optimize clinical trial outcomes for SFK inhibitor therapies.

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