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Regulators of the RAS-ERK pathway as therapeutic targets in thyroid cancer

Miguel A Zaballos1,2, Adrián Acuña-Ruiz1,2, Marta Morante2,3

  • 1Instituto de Investigaciones Biomédicas 'Alberto Sols', Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain.

Endocrine-Related Cancer
|April 13, 2019
PubMed

Insights

Thyroid cancer often involves the RAS/ERK pathway, but current treatments face resistance. Targeting other regulators in this complex pathway may offer new therapeutic strategies for advanced thyroid carcinomas.

Area of Science:

  • Oncology
  • Molecular Biology
  • Signaling Pathways

Background:

  • Thyroid cancer incidence is rising, with up to 70% driven by mutations activating the RAS/ERK pathway.
  • Current treatments targeting BRAF and MEK show limited clinical success due to tumor resistance and relapse.
  • The RAS/ERK pathway's complexity presents multiple potential therapeutic targets beyond BRAF and MEK.

Purpose of the Study:

  • To review the biology of RAS/ERK pathway regulators in human cancers.
  • To highlight specific information relevant to thyroid cancer.
  • To identify future research directions for targeting the RAS/ERK pathway in thyroid cancer.

Main Methods:

  • Literature review of RAS/ERK pathway biology and regulators.
  • Analysis of current therapeutic strategies and their limitations in thyroid cancer.
  • Identification of potential novel therapeutic targets within the RAS/ERK signaling cascade.

Main Results:

  • The RAS/ERK pathway is a critical driver in a majority of thyroid carcinomas.
  • Inhibitors targeting BRAF and MEK have shown limited efficacy in clinical settings.
  • Numerous regulatory points within the RAS/ERK pathway offer alternative therapeutic opportunities.

Conclusions:

  • Understanding the intricate regulation of the RAS/ERK pathway is crucial for developing effective treatments for advanced thyroid cancer.
  • Exploring novel targets, including RAS modulators, scaffolding proteins, and negative feedback mechanisms, is essential.
  • Further research into these regulators could overcome current therapeutic limitations and improve patient outcomes.
Keywords:
GEF/GAPMKPRAS/ERKscaffoldthyroid cancer

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