title: Tumor flare after start of RAF inhibition in KRAS mutated NSCLC: a case report.
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.
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wouter W
authors.initials: WW
authors.lastname: Mellema
authors.affiliation: Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Sjaak A
authors.initials: SA
authors.lastname: Burgers
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: ef.smit@vumc.nl.
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
mesh_terms: D000328:Adult; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins
keywords: KRAS mutation; Non-small cell lung cancer; Paradoxal activation; RAF inhibitor; Sorafenib; Tumor flare