Researchers have identified a promising approach for treating difficult-to-treat malignant peripheral nerve sheath tumors (MPNSTs) by using a combination of two experimental medications. The findings were reported in Molecular Cancer Therapeutics, highlighting how the duo works together to slow tumor growth and extend survival in preclinical models.
In a mouse study, the paired drugs targeted two separate metabolic vulnerabilities in cancer cells. One medicine interfered with how cancer cells use glutamine, an amino acid that supports energy production and rapid growth. The other medicine disrupted the recycling process that supplies purines, which are essential building blocks for DNA and RNA. When used together, these agents significantly reduced tumor size and improved survival compared with single-agent strategies, while showing a lower toxicity profile than traditional treatments.
Earlier work from the same research group had shown that blocking glutamine utilization alone could partially shrink tumors. However, malignant cells can compensate by salvaging purines through recycling pathways. The combination therapy is designed to cut off this escape route, depriving tumors of both critical supplies and thereby enhancing anti-tumor activity.
Glutamine serves as a versatile source of carbon and nitrogen for cancer cells, fueling protein synthesis and the creation of other large molecules needed for rapid growth and survival. By inhibiting glutamine metabolism, cancer cells face a bottleneck that slows proliferation and disrupts the pathways that support tumor maintenance, making them more susceptible to additional metabolic disruption. The second drug’s role is to prevent tumor cells from tapping into purine pools via salvage pathways, effectively limiting DNA and RNA synthesis required for tumor progression. In combination, these strategies create a metabolic squeeze that cancer cells have trouble overcoming.
Malignant peripheral nerve sheath tumors are rare cancers that arise from the protective sheaths surrounding peripheral nerves. The prognosis for individuals with MPNSTs depends on several factors, including whether complete surgical resection is possible, how the tumor responds to standard chemotherapy, and the extent to which the disease has spread. Current treatment options can be limited, and researchers continue to explore therapies that offer improved efficacy with manageable side effects. While this study centers on preclinical data, it provides a compelling rationale for advancing combination metabolic therapies into early-stage clinical evaluation as a potential option for patients with difficult-to-treat MPNSTs. Future work will focus on confirming safety and determining optimal dosing, as well as identifying biomarkers that predict which tumors are most likely to respond. [Citation: Molecular Cancer Therapeutics]