A recent paper in the Journal of Clinical Investigation identified targets for therapy of malignant peripheral nerve sheath tumors (MPNST) in patients with Neurofibromatosis type 1 (NF1). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras/Raf/MEK/ERK signaling. PD0325901, a highly selective pharmacological inhibitor of MEK, reduced aberrantly proliferating cells in neurofibroma and MPNST, prolonged survival of a mouse model of NF1 implanted with human MPNST cells, and shrank neurofibromas in more than 80% of mice tested. These data show that deregulated Ras/ERK signaling is critical for the growth of NF1 peripheral nerve tumors and provide a strong rationale for investigating MEK inhibitors in clinical trials.
OMMBID. Section 5: 39
Posted by Nicola Brunetti-Pierri, MD