Liver cancer is one of the world’s most common and lethal forms of cancer, primarily diagnosed at advanced stages, limiting therapeutic options.
Current first-line treatments offer minimal benefits, necessitating the exploration of effective alternatives.
Recent studies, including one by Dr. Hongbing Zhang and team from the Chinese Academy of Medical Sciences, focus on addressing hepatocellular carcinoma (HCC) through targeting the common mutation in the CTNNB1 gene, leading to excessive β-catenin and uncontrolled cell proliferation.
The Research
The study, published in the Chinese Medical Journal, investigated whether existing chemotherapy drugs could effectively treat β-catenin-activated liver cancer.
The team opted for drug repurposing as a strategy due to its advantages in reducing development costs and time.
The researchers screened 12 chemotherapeutic drugs, finding methotrexate (MTX), a drug typically used for conditions like rheumatoid arthritis and certain cancers, to be particularly effective against β-catenin-activated cells.
Method and Findings
Both genetically modified cells and mice with subcutaneous tumors expressing the mutated CTNNB1 gene were subjected to different chemotherapeutic drugs.
MTX displayed efficacy and selectivity on β-catenin-activated human liver cancer cells, both in vitro and in vivo.
Surprisingly, MTX did not directly impact β-catenin signaling but repressed β-catenin-induced nucleotide synthesis leading to malignancy, sensitizing the mutant cells to the treatment.
To mirror real-world clinical conditions more closely, the team generated mice models with HBV-induced chronic hepatitis and β-catenin activation, considering the significant role of HBV-induced chronic hepatitis as a major risk factor for HCC.
The results showed a notable reduction in tumor incidence and size in mice treated with MTX compared to untreated ones, with minimal effects on body weights.
Significance
The effectiveness of MTX against β-catenin-activated cells signifies its potential as an alternative therapeutic option for liver cancer involving the CTNNB1 mutation, particularly as existing treatments prove ineffectual.
MTX’s mechanism of inhibiting nucleotide metabolism highlights a novel pathway to counter β-catenin-induced malignancy without directly affecting β-catenin signaling.
Conclusion
Dr. Zhang’s research emphasizes the potential of methotrexate as a promising chemotherapeutic agent for β-catenin-hyperactive liver cancer.
The repurposing of MTX stands out due to lower risks, reduced investment, and shortened development timelines in drug discovery and development, making it a viable candidate for further clinical trials to ascertain its efficacy in treating β-catenin mutant liver cancer.
The study opens up new avenues in liver cancer treatment, hinting at more efficient, targeted therapeutic strategies against specific genetic abnormalities associated with the disease.
If you care about liver health, please read studies about This hormone can prevent fatty liver and findings of Scientists find new causes of liver and kidney failure.
For more information about health, please see recent studies about major cause of fatty liver disease, leaky gut, and results showing why a glass of red wine is good for your gut.
The research findings can be found in Chinese Medical Journal.
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