Abstract
Here we describe a case of striking tumor flare after start of treatment with sorafenib and metformin as part of a phase II clinical trial. Previous reports have described a paradoxal activation of the MAPK pathway after treatment with a weak RAF inhibitor. This mechanism is based on inhibition of a negative feedback loop to upstream effectors of RAF and subsequently increased stimulation of the RAS-RAF-MEK-ERK (MAPK) pathway. We suggest that sorafenib may contribute to tumor progression through this mechanism and clinicians should be aware of this phenomenon when treating NSCLC patients with sorafenib.
Keywords:
KRAS mutation; Non-small cell lung cancer; Paradoxal activation; RAF inhibitor; Sorafenib; Tumor flare.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
MeSH terms
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Adult
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Carcinoma, Non-Small-Cell Lung / drug therapy
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Carcinoma, Non-Small-Cell Lung / genetics*
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology*
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Disease Progression
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Female
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Humans
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Lung Neoplasms / drug therapy
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Lung Neoplasms / genetics*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology*
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Mitogen-Activated Protein Kinases / metabolism
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Mutation*
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Neoplasm Staging
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / adverse effects*
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
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Proto-Oncogene Proteins B-raf / metabolism
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Signal Transduction / drug effects
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Tomography, X-Ray Computed
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Tumor Burden
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ras Proteins / genetics*
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ras Proteins / metabolism
Substances
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins B-raf
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Mitogen-Activated Protein Kinases
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ras Proteins