MEK inhibitors lead to PDGFR pathway upregulation and sensitize tumors to RAF dimer inhibitors in NF1-deficient malignant peripheral nerve sheath tumor (MPNST).
Miguel A Miranda-RománCindy J LeeEve FishinevichLeili RanAmish J PatelJuan YanMakhzuna N KhudoynazarovaSarah WardaMohini R PachaiJuliet ChenPing ChiPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2024)
Our findings suggest that the combination of MEKi and PDGFR and/or RAF dimer inhibitors can overcome MEKi resistance and may serve as a novel targeted therapeutic strategy for NF1-deficient MPNST patients, which in turn could impact future clinical investigations for this patient population.