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Efficacy of MEK inhibition in a recurrent malignant peripheral nerve sheath tumor
Sumanth Nagabushan1,2, Loretta M S Lau1,2,3, Paulette Barahona3
1Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia.
Abstract:
The prognosis of recurrent malignant peripheral nerve sheath tumors (MPNST) is dismal, with surgical resection being the only definitive salvage therapy. Treatment with chemoradiation approaches has not significantly improved patient outcomes. Similarly, trials of therapies targeting MPNST genomic drivers have thus far been unsuccessful. Improved understanding of the molecular pathogenesis of MPNST indicates frequent activation of the mitogen-activated protein kinase (MAPK) cell signaling pathway. MEK inhibitors have shown activity in preclinical studies; however, their clinical efficacy has not been reported to date. We describe here a case of sustained complete response to MEK inhibition in an adolescent patient with a recurrent metastatic MPNST with multiple alterations in the MAPK pathway, guided by a precision oncology approach.
Insights
Malignant peripheral nerve sheath tumors (MPNST) are aggressive. A precision oncology approach using MEK inhibitors led to a sustained complete response in a patient with recurrent metastatic MPNST.
Area of Science:
- Oncology
- Molecular Pathology
- Genetics
Background:
- Recurrent malignant peripheral nerve sheath tumors (MPNST) have a poor prognosis.
- Current treatments like surgery, chemoradiation, and targeted therapies have limited success.
- The mitogen-activated protein kinase (MAPK) pathway is frequently activated in MPNST.
Purpose of the Study:
- To report a case of sustained complete response to MEK inhibition in a patient with recurrent metastatic MPNST.
- To highlight the potential of precision oncology in treating MPNST.
- To investigate the clinical efficacy of MEK inhibitors in MPNST.
Main Methods:
- A precision oncology approach was used, guided by genomic profiling.
- The patient received MEK inhibition therapy.
- The patient had a recurrent metastatic MPNST with MAPK pathway alterations.
Main Results:
- The adolescent patient achieved a sustained complete response.
- MEK inhibition demonstrated clinical efficacy in this MPNST case.
- The treatment was guided by the identification of multiple MAPK pathway alterations.
Conclusions:
- MEK inhibition can be an effective salvage therapy for recurrent metastatic MPNST.
- Precision oncology guided by molecular profiling offers a promising treatment strategy for MPNST.
- Targeting the MAPK pathway with MEK inhibitors warrants further clinical investigation in MPNST.
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