“Aramchol and metformin interacted to modestly enhance cell death in PDX UM cells, though this was less than that caused by the combination of aramchol and the multi-kinase inhibitor regorafenib. ”
BUFFALO, NY – March 31, 2026 – A new research paper was published in Volume 17 of Oncotarget on March 27, 2026, titled “ The SCD1 inhibitor aramchol interacts with regorafenib and metformin to kill tumor cells .”
Led by Michael R. Booth, Laurence Booth, and Jane L. Roberts from Virginia Commonwealth University , with corresponding author Paul Dent from the same institution and John M. Kirkwood from the University of Pittsburgh Cancer Institute , the study examines how aramchol interacts with regorafenib and metformin to kill tumor cells, particularly patient-derived uveal melanoma (UM) cells and cholangiocarcinoma cells.
The authors report that aramchol, regorafenib, and metformin interact to enhance tumor cell killing, with the strongest effects seen when metformin is added to aramchol plus regorafenib. In patient-derived UM cells and LD-1 cholangiocarcinoma cells, the three-drug combination increased autophagosome formation and autophagic flux, while knockdown of Beclin1, ATG5, or LAMP2 reduced autophagosome and autolysosome formation and lowered cell killing. The study also found that BID contributes to the lethal response, supporting a multifactorial mechanism involving macroautophagy and death-receptor signaling.
“ Our data demonstrates that UM cells are killed by treatment with aramchol plus regorafenib plus metformin via enhanced autophagic flux and that this combination may have the potential to control UM tumors that have metastasized to the liver.”
The authors also note that while SCD1 knockdown increased baseline tumor cell death, it did not replicate the full anticancer effects of aramchol, suggesting additional molecular targets contribute to its activity. They emphasize the need for further in vivo studies to evaluate the therapeutic potential of this combination in metastatic uveal melanoma, particularly in liver-targeted disease.
DOI: https://doi.org/10.18632/oncotarget.28861
Correspondence to: Paul Dent – paul.dent@vcuhealth.org
Abstract video: https://www.youtube.com/watch?v=lmX_c2e_-HY
Keywords : cancer, macroautophagy, ER stress, aramchol, regorafenib, BID
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The SCD1 inhibitor aramchol interacts with regorafenib and metformin to kill tumor cells
27-Mar-2026
PD has received support from Galmed Pharmaceuticals Inc. for these studies. Data is proprietary and is owned by VCU and Galmed Pharmaceuticals Ltd.