Marcus Smith Noel, MD
SM-88, a novel compound that attacks oncogenic metabolic pathways, is under development for patients with metastatic pancreatic cancer and other solid tumors, raising the potential for a tumor-agnostic therapy.
In the single-arm study, participants will receive SM-88 daily in an oral formulation. The drug consists of an investigational agent, the tyrosine derivative D,L-alphametyrosine, and 3 repurposed drugs: an mTOR inhibitor, sirolimus; a CYP3A4 inducer, phenytoin; and an oxidative stress catalyst, methoxsalen.
The compound seeks to exploit the Warburg effect, a metabolic process through which cancer cells use aerobic glycolysis to increase glucose uptake and fermentation to promote their own growth, survival, proliferation, and long-term maintenance.1
“The thought process is that D,L-alphametyrosine will essentially alter the metabolism of pancreatic cancer,” Marcus Smith Noel, MD, a leading investigator into SM-88, said in an interview with OncologyLive®. “All cancers are able to thrive in an oxidative environment…an environment that is deprived of nutrients and oxygen. This denatured agent plus the 3 other repurposed drugs are designed to capitalize on that, such that they’re going to increase uptake of D,L-metyrosine into the cell and, hopefully, that will result in cell death.”
Early Data Show Promise
Noel, an assistant professor at University of Rochester Medicine’s Wilmot Cancer Institute in New York, presented data from part 1 of Tyme- 88-Panc at the 2018 Gastrointestinal Cancers Symposium. Patients were randomly assigned to D,L-alpha-metyrosine at a twice-daily dosage of either 230 mg or 460 mg. In both arms, patients also received 10 mg/day of methoxsalen, 50 mg/ day of phenytoin, and 0.5 mg/day of sirolimus.
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