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Targeted inhibition of Src kinase with dasatinib blocks thyroid cancer growth and metastasis

Christine M Chan1, Xia Jing, Laura A Pike

  • 1Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|May 16, 2012
PubMed
Abstract

Insights

Src inhibitors like dasatinib show promise for treating thyroid cancer. This study found dasatinib effectively blocked papillary thyroid cancer (PTC) growth and metastasis in preclinical models, offering new therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) lack effective therapies, with bone metastasis indicating a poor prognosis.
  • Src family kinases (SFKs) are implicated in tumor progression and metastasis and are overexpressed in thyroid cancer.
  • Src inhibition presents a potential therapeutic strategy for thyroid cancer.

Purpose of the Study:

  • To investigate the efficacy of dasatinib, a Src inhibitor, in blocking thyroid cancer growth and metastasis.
  • To evaluate the effects of dasatinib on thyroid cancer cell signaling, cell cycle, and apoptosis.
  • To determine the role of Src in thyroid cancer progression.

Main Methods:

  • In vitro studies assessed dasatinib's effects on thyroid cancer cell growth, signaling, cell cycle, and apoptosis.
  • In vivo studies utilized orthotopic and experimental metastasis models to evaluate dasatinib's therapeutic efficacy.
  • Src family kinase expression and activation were characterized, and dasatinib's selectivity was tested using an Src gatekeeper mutant.

Main Results:

  • Dasatinib inhibited Src signaling, reduced growth, and induced cell-cycle arrest and apoptosis in a subset of thyroid cancer cells.
  • c-Src and Lyn were identified as key SFKs in thyroid cancer, with c-Src being predominantly activated.
  • Dasatinib treatment significantly inhibited papillary thyroid cancer tumor growth (over 90%) and metastasis in preclinical models.

Conclusions:

  • Src is a critical mediator of thyroid cancer growth and metastasis.
  • Src inhibitors, such as dasatinib, demonstrate potential as both antitumor and antimetastatic agents for thyroid cancer.
  • These findings support the clinical investigation of Src inhibitors for thyroid cancer treatment.

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