Related Experiment Video

Updated: May 10, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

Influence of RET mutations on the expression of tyrosine kinases in medullary thyroid carcinoma

Cristina Rodríguez-Antona1, Iván Muñoz-Repeto, Lucia Inglada-Pérez

  • 1Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, Madrid, Spain.

Endocrine-Related Cancer
|June 20, 2013
PubMed

Insights

Therapeutic options for metastatic medullary thyroid carcinoma (MTC) have expanded with tyrosine kinase inhibitors (TKIs). This study reveals varied TKI target protein expression in MTC, linked to RET mutations, suggesting personalized therapy potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Translational Research

Background:

  • Metastatic medullary thyroid carcinoma (MTC) treatment has advanced with tyrosine kinase inhibitors (TKIs).
  • Significant variability exists in patient responses to TKIs, with the underlying molecular basis largely unknown.
  • Understanding TKI target expression is crucial for optimizing MTC therapy.

Purpose of the Study:

  • To investigate the expression of eight key TKI target proteins in MTC.
  • To correlate protein expression with clinical and molecular features, including RET mutations.
  • To explore the potential for molecular stratification to improve TKI efficacy in MTC.

Main Methods:

  • Immunohistochemistry was used to assess the expression of EGFR, KIT, MET, PDGFRB, VEGF, VEGFR1, VEGFR2, and VEGFR3.
  • 103 molecularly characterized MTC samples were analyzed.
  • Expression data were correlated with RET mutation status and clinical characteristics.

Main Results:

  • High expression of VEGFR2 (57%) and VEGFR3 (43%) was observed in MTC samples.
  • Other TKI targets like VEGFR1, PDGFRB, VEGF, KIT, and MET showed variable expression (34-20%), with EGFR in 10%.
  • Specific RET mutations (C634) correlated with higher VEGFR3 and KIT expression and lower VEGFR1 expression, while non-mutated RET cases showed lower PDGFRB expression.

Conclusions:

  • Multiple TKI targets are highly expressed in a subset of MTC patients.
  • RET mutation status is associated with distinct immunohistochemical profiles of TKI targets.
  • Molecular stratification of MTC patients based on TKI target expression may enhance TKI therapy outcomes.
Keywords:
EGFRKITMETPDGFRBRET mutationVEGFVEGFR1VEGFR2VEGFR3medullary thyroid carcinomatyrosine kinase inhibitors

More Related Videos

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays07:42

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

Published on: September 19, 2018

Spontaneous Murine Model of Anaplastic Thyroid Cancer05:39

Spontaneous Murine Model of Anaplastic Thyroid Cancer

Published on: February 3, 2023

Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...