Effect of inhibition of the FGFR-MAPK signaling pathway on the development of ocular toxicities.

Abstract

By the introduction of molecularly targeted anti-cancer drugs, that are designed to intervene with specific pathways aberrant in cancers with distinct mutations, the type of adverse events encountered has changed greatly compared to the adverse events profile of classical chemotherapeutic agents. Ocular toxicities, such as serous retinal detachment and retinal vein occlusion, are observed in the treatment with several protein kinase inhibitors, such as MEK inhibitors. This review discusses the pathophysiology, diagnosis and advice for clinical management of these toxicities, and focuses on the current understanding of the underlying molecular mechanisms. Some ocular toxicities can be considered a class effect and a direct result of intervening with the MAPK pathway. Effective recording and monitoring will contribute to increased understanding of the prevalence and of adequate management of these ocular toxicities, but further research is warranted to elucidate the exact underlying mechanisms and to optimize treatment of these undesirable toxicities.

• Authors: Ruud van der Noll, Suzanne Leijen, Guido H G Neuteboom, Jos H Beijnen, Jan H M Schellens
• Journal: Cancer treatment reviews (Cancer Treat Rev) Vol. 39 Issue 6 Pg. 664-72 (Oct 2013) ISSN: 1532-1967 [Electronic] Netherlands
• PMID: 23434072 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Protein Kinase Inhibitors
• Receptor, Fibroblast Growth Factor, Type 1
• Mitogen-Activated Protein Kinases

Topics

• Eye Diseases (chemically induced)
• Humans
• MAP Kinase Signaling System (drug effects)
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Molecular Targeted Therapy (adverse effects, methods)
• Protein Kinase Inhibitors (adverse effects)
• Receptor, Fibroblast Growth Factor, Type 1 (antagonists & inhibitors, metabolism)
• Signal Transduction