Targeted therapies have provided the foundation for many advances in the treatment options for patients with late-stage cancer, however, adaptive and compensatory responses frequently limit their efficacy. Rational combinations of targeted inhibitors are being actively tested in preclinical models to form the basis for more durable responses in patients. In a previous issue, Wang and colleagues provide evidence that phosphorylated SHP2 is adaptively upregulated in response to MEK inhibitors in malignant peripheral nerve sheath tumors (MPNST) that have lost NF1 expression. The authors provide evidence that the combination of SHP2 inhibitors with MEK inhibitors has strong efficacy in preclinical MPNST models and propose that this targeted therapy combination should be rapidly translated.See related article by Wang et al.; Cancer Res 80(23):5367-79.
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