Aramchol Boosts Regorafenib Effectiveness in Gastrointestinal Tumors
Aug 19, 2025
Exploring an innovative combo therapy, researchers reveal how aramchol enhances the effectiveness of regorafenib against gastrointestinal tumors. This intriguing study showcases its potential to personalize cancer treatment by targeting specific genetic variants. Remarkably, the combination not only kills cancer cells more effectively but also demonstrates reduced side effects in animal models. Discover how this strategy could reshape liver and colorectal cancer therapies while offering hope for less toxic options.
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Drug Combination Enhances Tumor Kill
Aramchol combined with regorafenib kills GI tumor cells more effectively than either drug alone in cells and mouse models.
The combo slowed human liver tumor growth in mice without causing weight loss or obvious toxicity.
insights INSIGHT
Repurposing Metabolism Drug For Cancer
Aramchol, developed for fatty liver disease, alters cancer cell lipid and energy metabolism.
Targeting metabolism can sensitize tumors to established kinase inhibitors like regorafenib.
insights INSIGHT
Genetic Variant Predicts Response
The combination was especially effective in cells with the ATG16L1 T300 genetic variant.
That variant is more common in people of African ancestry and influenced treatment response.
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BUFFALO, NY – August 19, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 19, 2025, titled “The SCD1 inhibitor aramchol interacts with regorafenib to kill GI tumor cells in vitro and in vivo.”
In this study, led by first authors Laurence Booth and Michael R. Booth, along with corresponding author Paul Dent from Virginia Commonwealth University, researchers investigated how aramchol, a drug originally developed for liver disease, works with the cancer drug regorafenib in gastrointestinal (GI) tumor cells. They found that the combination is effective, especially in tumor cells with a specific genetic variant. The combined approach offers a potential new strategy for treating liver and colon cancers.
Gastrointestinal cancers, such as liver and colon cancer, are serious global health challenges. Regorafenib, already approved for cancer treatment, can have limited impact and frequently causes side effects. Aramchol, a drug developed to treat fatty liver disease, affects how cancer cells process fats and energy. In this study, researchers tested whether combining these two drugs could improve GI cancer treatment, both in cells and mouse models.
The results showed that the drug combination killed liver and colorectal cancer cells more effectively than either drug alone. In animal models, mice with human liver tumors had slower tumor growth, without showing signs of weight loss or other toxicity.
The researchers also found that aramchol and regorafenib work together to block important survival pathways inside cancer cells. This combination was especially effective in cells with a genetic variant called ATG16L1 T300, which is more common in people of African ancestry. The treatment triggered stress responses in the cancer cells and disrupted key proteins required for survival. It also activated autophagy, a natural recycling process that clears out damaged parts, eventually leading to cancer cell death.
“Aramchol interacted with the multi-kinase inhibitors sorafenib, regorafenib or lenvatinib, to kill GI tumor cells, with regorafenib exhibiting the greatest effect.”
Aramchol is currently in clinical trials for fatty liver disease and has a well-established safety profile, while regorafenib is already FDA-approved for cancer treatment. Together, their combination could advance fast into clinical testing for patients with GI cancers. However, researchers note that additional studies are needed to support the launch of early-phase clinical trials.
Altogether, this study may offer a more effective and less toxic alternative to current treatments for GI cancers. It also highlights the role of genetic variants in shaping treatment response, suggesting that future therapies could be more precisely tailored to each patient’s unique genetic profile.
DOI - https://doi.org/10.18632/oncotarget.28762
Correspondence to - Paul Dent - paul.dent@vcuhealth.org
Video short - https://www.youtube.com/watch?v=5saAqsqxi-Q
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Keywords - cancer, macroautophagy, flux; ER stress, aramchol, regorafenib
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