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Lung Cancer. 2015 Feb;87(2):201-3. doi: 10.1016/j.lungcan.2014.11.014. Epub 2014 Nov 29.

Tumor flare after start of RAF inhibition in KRAS mutated NSCLC: a case report.

Author information

1
Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands.
2
Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
3
Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: ef.smit@vumc.nl.

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

PMID:
25488861
DOI:
10.1016/j.lungcan.2014.11.014
[Indexed for MEDLINE]

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