Trio of Drugs Shows Promise for Treating Uveal Melanoma

Aramchol, regorafenib, and metformin combination enhances tumor cell killing in patient-derived samples.

Apr. 1, 2026 at 5:02am

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A translucent, ghostly X-ray-style image showing the internal structures of the human eye, including the iris, retina, and optic nerve, conceptually representing the impact of uveal melanoma on the eye.An X-ray-like image reveals the internal structures of the eye affected by uveal melanoma, a rare and aggressive form of eye cancer.Buffalo Today

A new study published in Oncotarget examines how the combination of the SCD1 inhibitor aramchol, the multi-kinase inhibitor regorafenib, and the diabetes drug metformin can effectively kill tumor cells, particularly in patient-derived uveal melanoma (UM) and cholangiocarcinoma samples. The three-drug regimen was found to increase autophagosome formation and autophagic flux, leading to enhanced tumor cell death.

Why it matters

Uveal melanoma is a rare and aggressive form of eye cancer that often metastasizes to the liver, making it difficult to treat. This new drug combination could offer a potential new therapeutic approach for controlling metastatic uveal melanoma, especially in the liver.

The details

The study, led by researchers from Virginia Commonwealth University and the University of Pittsburgh Cancer Institute, found that aramchol and metformin had a modest interaction in enhancing cell death in patient-derived UM cells. However, the combination of aramchol, regorafenib, and metformin produced the strongest anticancer effects. The three-drug regimen increased autophagosome formation and autophagic flux, which was reduced when key autophagy genes were knocked down. The researchers also found that the pro-apoptotic protein BID contributed to the lethal response, suggesting a multifactorial mechanism involving both autophagy and death-receptor signaling.

  • The study was published on March 27, 2026 in Volume 17 of the journal Oncotarget.

The players

Michael R. Booth

Researcher from Virginia Commonwealth University and lead author of the study.

Laurence Booth

Researcher from Virginia Commonwealth University and co-author of the study.

Jane L. Roberts

Researcher from Virginia Commonwealth University and co-author of the study.

Paul Dent

Corresponding author of the study and researcher from Virginia Commonwealth University.

John M. Kirkwood

Researcher from the University of Pittsburgh Cancer Institute and co-author of the study.

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What they’re saying

“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.”

— Paul Dent, Corresponding author

What’s next

The authors emphasize the need for further in vivo studies to evaluate the therapeutic potential of this three-drug combination in metastatic uveal melanoma, particularly in liver-targeted disease.

The takeaway

This new research suggests a promising treatment approach for the difficult-to-treat uveal melanoma, especially in cases where the cancer has spread to the liver. The combination of aramchol, regorafenib, and metformin appears to effectively kill tumor cells through enhanced autophagy and other mechanisms, offering hope for improved outcomes for patients with this rare and aggressive form of eye cancer.