Cited 18 times since 2014 (1.9 per year) source: EuropePMC Lung cancer (Amsterdam, Netherlands), Volume 87, Issue 2, 29 5 2014, Pages 201-203 Tumor flare after start of RAF inhibition in KRAS mutated NSCLC: a case report. Mellema WW, Burgers SA, Smit EF
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.
