RICHMOND, Va. — Nov. 9, 2026 — Researchers from VCU Massey Comprehensive Cancer Center recently exhibited that the inhibition of glucosylceramide synthase (GCS) can cause death in cancer cells that is independent of changes in pro-death ceramide levels. The findings, which were recently published in Cell Death Discovery , found that utilizing eliglustat, an FDA-approved drug, induced cell death in several cancer cell lines. Additionally, the findings demonstrated, for the first time, that GCS and its products had a pro-survival role in cancer cells.
“This is exciting, because it has clinical impact,” said Alexandra Straus, Ph.D. , a post-doctoral fellow in the VCU Department of Cellular, Molecular and Genetic Medicine, who is also a collaborator on the paper. “As scientists that are at the bench, it’s important to think about how a clinical trial might be working, and these findings can help us identify potential biomarkers for understanding which patients might benefit most.”
Researchers in the lab of Can Senkal, Ph.D. , interim director of the Lipidomics and Metabolomics Shared Resource and member of the Cancer Biology research program at Massey, treated cancer cell lines that represent primary focuses in Massey’s catchment area - colon, ovarian and cervical cells - with eliglustat, a known inhibitor of GCS.
Eliglustat is typically used for the treatment of Gaucher disease type 1, a disease that occurs when a person has too little of the enzyme that breaks down glucosylceramide.
They found that eliglustat caused the cancer cells to die, not through ceramide accumulation as previously thought, but rather decreasing glucosylceramide in the cells. Further study by the Massey team showed that the cancer cells initially treated with eliglustat caused lysosomes to appear as enlarged vesicles because they could not degrade any cellular materials.
Because cancer cells rely on lysosomes to recycle cellular components, researchers showed that by inhibiting GCS via eliglustat, lysosomes cannot function properly, thereby inducing cancer cell death.
“Healthy cells need to have proper lysosomal function,” Senkal explained. “And cancer cells, since they grow so fast, they depend on this degradation process, so they need a healthy lysosome to keep up with their growth needs. And we think GCS or the complex glycosphingolipids have a role in maintaining the proper function of the lysosomes.
“And so, when the cancer cells do not have the GCS, they do not have the properly functioning lysosomes, and therefore, they die.”
These findings could have clinical impact in several ongoing clinical trials that feature eliglustat in combination with immunotherapy. Additionally, this research could be used to develop biomarkers for patients and in determining cancer cell signatures in which these findings can best be applied.
Researchers from Massey’s Cancer Biology and Development Therapeutics research programs are working to identify opportunities to further this research, likely by collaborating with outside companies or partners for clinical-grade compounding before further study could offer the opportunities for clinical trials.
Additionally, analysis of patient metabolites could provide a mechanism through which biomarker developments could be made in order to determine which patients have the lipid profile that might benefit from eliglustat.
Cell Death Discovery
Targeting glucosylceramide generation induces cancer cell death through lysosomal dysfunction independent of ceramide accumulation
22-Aug-2026