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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

Targeting RET receptor tyrosine kinase activation in cancer

John E Phay1, Manisha H Shah

  • 1Department of Surgery, Division of Surgical Oncology, The Ohio State University, Columbus, Ohio, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|October 9, 2010
PubMed

Insights

RET receptor tyrosine kinase mutations drive thyroid cancers. Small-molecule tyrosine kinase inhibitors show modest but significant promise for treating advanced medullary thyroid cancer (MTC), offering new hope.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • The RET receptor tyrosine kinase plays a crucial role in cell signaling pathways.
  • Activating RET mutations and rearrangements are key drivers in medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC).
  • RET alterations are implicated in Multiple Endocrine Neoplasia type 2 (MEN2) syndromes, necessitating early intervention.

Purpose of the Study:

  • To review the role of RET in thyroid cancer development and progression.
  • To evaluate the therapeutic potential of small-molecule tyrosine kinase inhibitors (TKIs) targeting RET in metastatic MTC.
  • To assess the clinical evidence for specific RET-targeting TKIs in MTC treatment.

Main Methods:

  • Review of scientific literature on RET signaling in thyroid cancer.
  • Analysis of clinical trial data for small-molecule TKIs targeting RET.
  • Examination of the efficacy of inhibitors like sorafenib, vandetanib, motesanib, sunitinib, and XL-184.

Main Results:

  • RET mutations and rearrangements are significant oncogenic events in MTC and PTC.
  • Small-molecule TKIs targeting RET demonstrate efficacy against various malignancies.
  • Initial clinical trials indicate that several TKIs offer some benefit in treating progressive metastatic MTC.

Conclusions:

  • Targeting RET with small-molecule TKIs represents a promising therapeutic strategy for advanced MTC.
  • Despite modest initial success, these inhibitors mark a significant advancement for patients with widespread metastatic MTC.
  • Early identification of germline RET mutations allows for timely prophylactic thyroidectomy in MEN2 patients.

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