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San Antonio, Texas – A groundbreaking new drug candidate may offer a safer and more effective treatment for metabolic dysfunction-associated steatotic liver disease (MASLD) and liver cancer, according to a study published on January 31, 2024, in Nature Aging.
San Antonio has one of the highest rates of MASLD in the United States, primarily due to high obesity and diabetes rates. This chronic liver condition can lead to severe fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), the most common form of liver cancer. Currently, there is no FDA-approved therapy that effectively slows the progression of MASLD and inhibits liver cancer development, making this research a significant breakthrough.
A New Approach to Treating Liver Disease
The study, led by Dr. Zhou, a tenured professor of biochemistry and structural biology at UT Health San Antonio, introduces a novel senolytic drug designed to selectively eliminate senescent cells—often referred to as “zombie cells.” These dysfunctional cells no longer divide but secrete harmful compounds that contribute to disease progression.
“Liver disease, particularly MASLD and hepatocellular carcinoma, disproportionately affects communities in San Antonio, where obesity and diabetes rates are high. Our study provides a promising path toward safer and more effective treatments for these diseases,” said Dr. Zhou.
How the Drug Works
Senolytics are drugs that selectively remove senescent cells to mitigate disease progression. While previous senolytic therapies have shown promise, none have been FDA-approved for human use due to toxicity concerns.
The new drug candidate developed by Dr. Zhou and his team works by degrading two proteins, BCL-xl and BCL-2, which help senescent cells survive and contribute to MASLD progression. By eliminating these proteins, the drug prompts senescent cells to self-destruct. This approach also weakens and destroys tumors that rely on these proteins for growth and survival.
Preclinical Findings Show Promise
Tests on cell cultures and a mouse model for MASLD demonstrated that the new drug was more powerful and selective than its predecessors. The results showed significant reductions in liver fat accumulation, inflammation, and fibrosis. Furthermore, in mice with advanced MASLD, the treatment reduced both the number and size of liver tumors, indicating its potential to prevent liver cancer.
Importantly, the study found that while the drug was effective in preventing liver cancer development, it was only beneficial against established tumors that depended on BCL-xl/BCL-2 proteins.
Potential Advantages Over Existing Treatments
Unlike traditional senolytics that indiscriminately remove all senescent cells—some of which play a role in tissue repair—this new drug specifically targets harmful senescent cells in the liver. This selectivity reduces the risk of side effects, such as impaired wound healing and organ dysfunction.
“This breakthrough in targeted senolytic therapy opens the door to developing even more selective and less toxic drugs. Moving forward, we aim to refine these treatments to tackle a wider range of liver diseases and potentially other age-related conditions, ensuring broader clinical impact,” said Dr. Zhou.
Looking Ahead
The research team plans further studies to assess the drug’s long-term safety and effectiveness in human clinical trials. If successful, this could represent a major step forward in addressing the growing public health burden of MASLD and liver cancer.
For more information, refer to the full study: Yang Yang et al, A BCL-xL/BCL-2 PROTAC effectively clears senescent cells in the liver and reduces MASH-driven hepatocellular carcinoma in mice, Nature Aging (2025). DOI: 10.1038/s43587-025-00811-7.
Disclaimer:
This article is based on preclinical research, and the drug candidate has not yet been approved for human use. The effectiveness and safety of this treatment in humans remain to be determined through clinical trials. Readers should consult medical professionals for health-related advice and rely on FDA-approved treatments for managing MASLD and liver cancer.
