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Targeting MAPK (Ras/ERK) and PI3K/Akt pathways in pituitary tumorigenesis

Mehtap Cakir1, Ashley B Grossman

  • 1Selcuk University, Meram School of Medicine, Division of Endocrinology and Metabolism, 42080, Meram, Konya, Turkey. cakirmehtap@yahoo.com

Expert Opinion on Therapeutic Targets
|July 30, 2009
PubMed
Abstract

Insights

Pituitary tumors may involve the Ras/extracellular signal-regulated protein kinase (ERK) and PI3K/Akt pathways. Further research into these signaling pathways could reveal new therapeutic strategies for pituitary tumors.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Pituitary adenomas represent 10-15% of primary brain tumors.
  • Autopsy data suggests a 17-25% prevalence of pituitary adenomas in the general population.
  • The exact pathogenesis of sporadic pituitary tumors remains largely unknown.

Purpose of the Study:

  • To review the involvement of MAPK (Ras/ERK) and PI3K/Akt signaling pathways in pituitary tumorigenesis.
  • To summarize current understanding of these molecular pathways in the context of pituitary tumor development.

Main Methods:

  • Comprehensive literature search of PubMed (2000-2009) and prior relevant publications.
  • Keywords included: pituitary, pituitary tumor, molecular biology, Akt, MAPK, PI3K, ERK.
  • Exclusion of studies on growth factor receptor mutations, G protein mutations, other signaling pathways, and genetic syndromes.

Main Results:

  • Preclinical data indicates potential involvement of Ras/ERK signaling in pituitary tumors.
  • Human pituitary tumor studies suggest a possible role for increased PI3K/Akt pathway activity.
  • Evidence supports the compatibility of increased Ras/ERK and/or PI3K/Akt pathway activity in pituitary tumors.

Conclusions:

  • Increased activity in Ras/ERK and/or PI3K/Akt pathways is supported by preclinical and clinical data in pituitary tumors.
  • Future research should focus on scaffold proteins and signaling modulators.
  • Identifying initiating events may lead to novel therapeutic strategies targeting these pathways.

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