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 a...

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Bibliographic Details
Published in:Cancer treatment reviews 2013-10, Vol.39 (6), p.664-672
Main Authors: van der Noll, Ruud, Leijen, Suzanne, Neuteboom, Guido H.G, Beijnen, Jos H, Schellens, Jan H.M
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Diagnosis
Eye Diseases - chemically induced
FGFR
Hematology, Oncology and Palliative Medicine
Humans
MAP Kinase Signaling System - drug effects
MAPK
Medical sciences
Mitogen-Activated Protein Kinases - antagonists & inhibitors
Mitogen-Activated Protein Kinases - metabolism
Molecular Targeted Therapy - adverse effects
Molecular Targeted Therapy - methods
Monitoring
Ocular toxicity
Pharmacology. Drug treatments
Protein Kinase Inhibitors - adverse effects
Receptor, Fibroblast Growth Factor, Type 1 - antagonists & inhibitors
Receptor, Fibroblast Growth Factor, Type 1 - metabolism
RVO
Signal Transduction
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Summary: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.
ISSN:0305-7372
1532-1967
DOI:10.1016/j.ctrv.2013.01.003