Mekininst for lung cancer – pro
The MEK protein kinases are downstream of KRAS and BRAF in the RAS/RAF/MEK/ERK pathway, also known as the MAP kinase cascade. Several small molecules have been developed to selectively inhibit MEK. However, despite preclinical activity, the clinical outcomes with these agents were not as promising, including CI-1040, RO5126766, and PD-0325901.
Rinehart J, Adjei AA, Lorusso PM, et al. Multicenter phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small-cell lung, breast, colon, and pancreatic cancer. J Clin Oncol. 2004;22:4456–4462.
Martinez-Garcia M, Banerji U, Albanell J, et al. First-in-human, phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of RO5126766, a first-in-class dual MEK/RAF inhibitor in patients with solid tumors. Clin Cancer Res. 2012;18:4806–4819. [PubMed]
Leijen S, Middleton MR, Tresca P, et al. Phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of the MEK inhibitor RO4987655 (CH4987655) in patients with advanced solid tumors. Clin Cancer Res. 2012;18:4794–4805.
Haura EB, Ricart AD, Larson TG, et al. A phase II study of PD-0325901, an oral MEK inhibitor, in previously treated patients with advanced non-small cell lung cancer. Clin Cancer Res. 2010;16:2450–2457.