Trametinib with or without Vemurafenib in BRAF Mutated Non-Small Cell Lung Cancer

• DOI: 10.1371/journal.pone.0118210
• Publication Date: 2015-02-23T19:23:03Z
• Authors: Monika Joshi; Shawn J. Rice; Xin Liu; Bruce Miller; Chandra P. Belani
• Keywords: Trametinib; V600E; Erlotinib Hydrochloride

V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutated lung cancer is relatively aggressive and resistant to currently available therapies. In a recent phase II study for patients with BRAF-V600E non-small cell (NSCLC), BRAF V600E inhibitor demonstrated evidence of activity, but 30% this selected group progressed while on treatment, suggesting need developing alternative strategies. We tested two different options enhance the efficacy vemurafenib (BRAF inhibitor) in NSCLC. The first option was addition erlotinib see whether combination provided synergy. second induce MEK inhibition (downstream RAF) trametinib (MEK inhibitor). found that not synergistic p-ERK signaling cells. Vemurafenib caused significant apoptosis, G1 arrest upregulation BIM BRAF-V600 Trametinib effective as single agent cells, either or non-V600E. Finally, small increase apoptosis well when compared agent. Thus, hinting at possibility utilizing combinational approach management patients. Importantly, alone p-AKT non-V600 effect nullified combination. This finding suggests that, will be more efficacious clinical setting