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Updated: Mar 15, 2026

Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice
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Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice

Published on: December 21, 2019

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PI3 Kinase Pathway and MET Inhibition is Efficacious in Malignant Pleural Mesothelioma

Rajani Kanteti1, Jacob J Riehm1, Immanuel Dhanasingh1

  • 1Department of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL, USA.

Scientific Reports
|September 14, 2016
PubMed

Insights

Combining MET and PI3K inhibitors like crizotinib and BKM120 shows strong efficacy against malignant pleural mesothelioma (MPM). This dual-targeting approach effectively suppresses tumor growth and migration, offering a promising therapeutic strategy for MPM patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Malignant pleural mesothelioma (MPM) is an aggressive cancer often linked to asbestos exposure.
  • Overexpression and activation of MET and PI3K signaling pathways are common in MPM.
  • Targeting these pathways presents a potential therapeutic avenue for MPM.

Purpose of the Study:

  • To investigate the combined therapeutic effects of MET/ALK inhibitor crizotinib with PI3K inhibitors (BKM120 or GDC-0980) in MPM.
  • To evaluate the impact of these combinations on MPM cell viability, migration, and cell cycle.
  • To assess the in vivo efficacy of crizotinib and BKM120 combination in a patient-derived xenograft (PDX) mouse model.

Main Methods:

  • MPM cell lines were treated with individual and combination therapies (crizotinib, BKM120, GDC-0980).
  • Cell viability, migration, and apoptosis assays were performed.
  • Western blotting was used to assess protein phosphorylation (MET, AKT, S6K).
  • A PDX mouse model was utilized to evaluate in vivo tumor growth inhibition.

Main Results:

  • Individual and combination treatments significantly reduced MPM cell viability and migration.
  • Combinations demonstrated synergistic effects on growth inhibition and migration.
  • BKM120, alone or with crizotinib, induced G2-M cell cycle arrest and apoptosis.
  • In vivo studies showed significant synergistic tumor growth inhibition with crizotinib and BKM120.

Conclusions:

  • Dual inhibition of the MET and PI3K pathways is a highly effective strategy for MPM treatment.
  • Combination therapy with crizotinib and BKM120 shows significant synergistic efficacy.
  • Targeting both MET and PI3K pathways offers a superior therapeutic approach compared to single-agent treatments for MPM.

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