image: Figure 11: Aramchol and regorafenib interact to suppress tumor growth in vivo. (A) Studies were performed per USDA regulations under approved VCU IACUC protocol AD20008. HuH7 adult hepatoma cells (2 × 106) were injected into the left rear and right rear flanks of male NRG mice. Over two weeks, tumors formed: mean volume 130 ± 10 mm3. Animals were treated with vehicle control or with drugs IP daily; aramchol (50 mg/kg), regorafenib (10 mg/kg) or the drugs in combination. Tumor volumes were calculated on the indicated days using the formula (length – longest diameter) × (width)2/2 (n = 20 ± SD) *p < 0.05 less than vehicle control; **p < 0.05 less than aramchol as a single agent. (B) Mouse body mass was determined daily and is presented for those days when tumor volumes were, in parallel, being determined (n = 10 ± SD). There was no significant alteration in mouse body mass over the time course, p > 0.05.
Credit: Copyright: © 2025 Booth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“We determined in GI tumor cells that regorafenib interacted with aramchol to promote tumor cell killing.”
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.
Continue reading: DOI: https://doi.org/10.18632/oncotarget.28762
Correspondence to: Paul Dent – paul.dent@vcuhealth.org
Keywords: cancer, macroautophagy, flux, ER stress, aramchol, regorafenib
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Journal
Oncotarget
Method of Research
News article
Subject of Research
Not applicable
Article Title
The SCD1 inhibitor aramchol interacts with regorafenib to kill GI tumor cells in vitro and in vivo
Article Publication Date
19-Aug-2025
COI Statement
PD has received support from Galmed Pharmaceuticals Inc. for these studies. Dr. Baharaff is a paid officer of the company.