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Updated: Feb 14, 2026

The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
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The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers

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Preclinical evaluation and reverse phase protein Array-based profiling of PI3K and MEK inhibitors in endometrial

Ozlem Aslan1, Mattia Cremona2, Clare Morgan2

  • 1Department of Medical Oncology, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. ozlemasl@gmail.com.

BMC Cancer
|February 11, 2018
PubMed
Abstract

Insights

Targeting the phosphoinositide-3-kinase (PI3K) and RAS/MAPK pathways shows promise in endometrial cancer (EC). MEK inhibition is effective for KRAS-mutated and PTEN-retained EC, with potential biomarkers identified.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • The phosphoinositide-3-kinase (PI3K) pathway is frequently activated in cancers, including endometrial cancer (EC).
  • Mutations in PI3K and RAS/RAF/MEK/MAPK (RAS/MAPK) pathways often co-occur in EC.
  • PTEN loss is a common event contributing to PI3K pathway activation.

Purpose of the Study:

  • To investigate the role of PI3K and RAS/MAPK pathway mutations in EC.
  • To determine the responsiveness of EC cell lines to targeted therapies against PI3K and MEK pathways.
  • To identify potential biomarkers for predicting treatment response.

Main Methods:

  • Profiling of 13 EC cell lines for PI3K pathway, KRAS mutations, and PTEN protein status.
  • Treatment with MEK and PI3K inhibitors, alone and in combination.
  • Analysis of signaling pathway changes using Reverse-Phase-Protein-Array (RPPA).

Main Results:

  • PTEN loss and absence of mutations predicted poor response to MEK inhibition.
  • KRAS-mutated cells were sensitive to MEK inhibitors but resistant to PI3K inhibitors.
  • Combinations of PI3K and MEK inhibitors demonstrated synergy or additivity in most cell lines.
  • Feedback activation of MEK/MAPK and AKT pathways was observed in response to PI3K and MEK inhibition, respectively.

Conclusions:

  • MEK inhibition is a potential treatment for EC, particularly for tumors with mutated KRAS or retained PTEN.
  • Up-regulation of MEK/MAPK and AKT signaling may serve as predictive biomarkers for PI3K and MEK inhibitors, respectively.
  • Targeting these pathways offers a promising therapeutic strategy for endometrial cancer.
Keywords:
BiomarkersEndometrial cancerKRASMEK inhibitorPI3K inhibitorPIK3CAPTEN lossProtein signalling

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