Searching for targets for the systemic therapy of mesothelioma

Ann Oncol. 2015 Aug;26(8):1649-60. doi: 10.1093/annonc/mdv101. Epub 2015 Feb 26.

Abstract

Malignant mesothelioma is an incurable disease associated with asbestos exposure arising in the pleural cavity and less frequently in the peritoneal cavity. Platinum-based combination chemotherapy with pemetrexed is the established standard of care. Multimodality approaches including surgery and radiotherapy are being investigated. Increasing knowledge about the molecular characteristics of mesothelioma had led to the identification of novel potential targets for systemic therapy. Current evidence suggests pathways activated in response to merlin deficiency, including Pi3K/mTOR and the focal adhesion kinase, as well as immunotherapeutic approaches to be most promising. This review elaborates on the rationale behind targeted approaches that have been and are undergoing exploration in mesothelioma and summarizes available clinical results and ongoing efforts to improve the systemic therapy of mesothelioma.

Keywords: immunotherapy; mesothelioma; targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage
  • Everolimus / administration & dosage
  • Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Humans
  • Immunotherapy
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Mesothelioma / drug therapy*
  • Mesothelioma / metabolism
  • Mesothelioma, Malignant
  • Molecular Targeted Therapy / methods*
  • Pemetrexed / administration & dosage
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Pleural Neoplasms / drug therapy*
  • Pleural Neoplasms / metabolism
  • Protein Kinase Inhibitors / administration & dosage
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Pemetrexed
  • Everolimus
  • Focal Adhesion Protein-Tyrosine Kinases
  • TOR Serine-Threonine Kinases
  • Cisplatin