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Medullary thyroid cancer: molecular biology and novel molecular therapies

Mehtap Cakir1, Ashley B Grossman

  • 1Centre for Endocrinology, Barts and the London School of Medicine, London, UK.

Neuroendocrinology
|May 27, 2009
PubMed

Insights

Medullary thyroid cancer (MTC) involves the RET proto-oncogene. Novel therapies like tyrosine kinase inhibitors show promise but require further development for better efficacy in treating MTC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Medullary thyroid cancer (MTC) originates from thyroid C cells, representing about 4% of all thyroid cancers.
  • MTC can be inherited (25-30% of cases) or sporadic.
  • The RET proto-oncogene plays a crucial role in both hereditary and sporadic MTC.

Purpose of the Study:

  • To review the structure, signaling, and role of the RET proto-oncogene in MTC.
  • To discuss novel therapies for metastatic MTC, focusing on tyrosine kinase inhibitors.
  • To summarize ongoing clinical trials and identify needs for improved treatments.

Main Methods:

  • Comprehensive literature search of PubMed (2000-2008) using keywords: 'medullary thyroid cancer, treatment, molecular biology, RET, molecular mechanism'.
  • Inclusion of relevant publications, including selected earlier works.
  • Review of data on tyrosine kinase inhibitors and ongoing clinical trials.

Main Results:

  • The RET proto-oncogene's wild-type and mutant forms are central to MTC development.
  • Tyrosine kinase inhibitors (e.g., vandetanib, sorafenib, sunitinib) targeting RET show activity in metastatic MTC.
  • Monotherapy with these inhibitors yields limited partial responses and no complete responses.

Conclusions:

  • While RET-targeting tyrosine kinase inhibitors offer a promising therapeutic avenue for MTC, their current efficacy is limited.
  • There is a significant need for novel therapeutic agents or combinations with improved efficacy and acceptable toxicity profiles for MTC treatment.

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