Posted on 09/26/2023 2:12:00 PM PDT by ConservativeMind
Liver cancer is one of the most deadly types of cancer worldwide. Most patients are diagnosed at an advanced stage, which leaves them with few treatment options. Unfortunately, the first-line drugs are not very effective and offer only modest clinical benefits.
Over the past few years, scientists have been trying to develop new therapies for HCC by analyzing specific genetic abnormalities. One of the most common mutations in HCC occurs in CTNNB1 gene, which encodes a protein called β-catenin.
However, no therapies targeting β-catenin-related pathways have been approved yet.
With this goal, the researchers first conducted a screening experiment using 12 widely used chemotherapeutic drugs. Employing both genetically modified cells in culture and mice inoculated with subcutaneous tumors expressing the mutated CTNNB1 gene, they found that methotrexate (MTX), a widely used drug for treating conditions such as psoriasis, rheumatoid arthritis, and certain types of cancer, was particularly effective against β-catenin-activated cells.
The efficacy and selectivity of MTX were further validated on β-catenin-activated human liver cancer cells in vitro and in vivo.
The analysis of changes produced by this drug revealed that it represses β-catenin-boosted nucleotide synthesis that leads to malignancy.
"MTX, a folic acid antagonist, is an inhibitor of nucleotide metabolism. It blocks the conversion of dihydrofolate to tetrahydrofolate, thereby hindering nucleotide synthesis in proliferating cancer cells," explains Dr. Zhang. Further experiments showed that the dysregulated β-catenin-activated nucleotide synthesis itself sensitizes the mutant cells to MTX treatment in the first place.
HBV (hepatitis B virus)-induced chronic hepatitis is the major risk factor of HCC. To make the animal model experiments more clinically relevant, the researchers generated mice with HBV transgenic and β-catenin activation livers. After three months, mice treated with MTX had remarkably lower tumor incidence, smaller maximum tumor volumes, and minimal effects on body weights compared to untreated mice.
(Excerpt) Read more at medicalxpress.com ...
I just noticed a prescription for methotrexate costs $2.50, on GoodRX.
It’s usually the cheapest treatment for autoimmune disorders as well.
Low Dose Naltrexone. For both. Cheap. Works for autoimmune. Some evidence for cancer.
As always, genetics plays a role in how well it works on someone.
btw, I refuse to take methotrexate right now because my biomarkers arent severe enough to take the risk for side effects.
However, LDN does take experimentation to figure out what dose works for you. Off label use.
What side effects? I’m been on methotraxate for over a year for my necrotizing autoimmune myopathy. Dr. had me get a liver scan beforehand to use as a baseline so I assume it’s liver related.
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