In a new study from Netherlands Cancer Institute and elsewhere, researchers found that insensitivity to a liver cancer drug can be prevented if it is given in combination with a second drug.
More and more cancer drugs—known as targeted therapy—inhibit the effects of DNA errors in the cancer cell. Unfortunately, cancer cells often are—or become—resistant to these drugs. They then continue to divide via an alternative signaling route in the cell.
In the study, the team exposes these routes in cancer cells by blocking all routes off, one by one, using genetic techniques such as CRISPR/Cas.
They discovered why the drug lenvatinib, one of the few targeted drugs on the market for liver cancer, shows no effect at all in 75-80% of patients.
The interferer turned out to be EGFR, a growth factor receptor, that—as the researchers observed—is activated in liver cancer cells as soon as the drug lenvatinib is administered, thereby spurring cell division.
In mouse models, the researchers then found that precisely those tumors that were resistant to lenvatinib from the start, did indeed activate the EGFR.
But they also discovered that it is possible to override this resistance in cells as well as mice by combining lenvatinib with another drug, gefitinib, which inhibits EGFR.
This is an existing drug that is already being used to treat lung cancer, for example.
Liver cancer is relatively rare in the West, although certain lifestyle factors have led to an increase in its occurrence.
In Africa and Asia, however, liver cancer, mainly as a result of hepatitis B and C, is a major problem, and half of the world’s deaths related to liver cancer occur in China.
The researchers were able to immediately set up a first-in-human clinical study at the Eastern Hepatobiliary Surgery Hospital in Shanghai. This hospital alone has 600 beds for patients with liver cancer.
This phase 1 proof-of-concept study involved twelve patients who previously did not respond to treatment with lenvatinib and who had large amounts of EGFR in their tumor.
A strong reduction of the tumor was observed in four of the twelve. The cohort of patients is now being expanded to thirty. After that, larger clinical studies are needed before this combination therapy can be used in the clinic.
The team says this study shows that it is possible to improve existing drugs by combining them. Another advantage is that gefitinib is off-patent, making it affordable.
If you care about liver health, please read studies about a big cause of leaky gut, fatty liver disease and findings of this dietary supplement may help treat fatty liver disease.
For more information about liver disease, please see recent studies about this common soap additive may worsen fatty liver disease and results showing that these two wholegrain foods may reduce weight gain and liver inflammation.
The study is published in Nature. One author of the study is Rene Bernards.
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