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Smart combination therapy for liver cancer tackles drug resistance

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Liver cancer is one of the most common types of cancer in the world, especially in China. A collaborative effort between researchers at the Dutch Cancer Institute and Shanghai using CRISPR / Cas has found that a liver cancer drug in combination with a second drug can prevent insensitivity.

Find alternative pathways for cancer cells

Gradually Anti-cancer agentSuppresses the effects of DNA errors — known as targeted therapies — cancer cell. Unfortunately, cancer cells are often resistant to or become resistant to these drugs. They then continue to divide via intracellular alternative signaling pathways. Molecular cancer researcher Rene Bernards has revealed these pathways in cancer cells by blocking all pathways one at a time using genetic techniques such as CRISPR / Cas.

Bernards first discovered one of these routes in 2012. He wanted to know why certain drugs do nothing for certain forms of colon cancer that are difficult to treat, while working well for melanoma with the exact same DNA mutation. He then realized that combining the first and second drugs would block this pathway. This was an innovative discovery that led to a longevity combination. Treatment It is currently used all over the world. It has also led to the search for other alternative signaling pathways and new combination therapies for other types of cancer.

Liver cancer combination therapy overcomes resistance

This week, Bernards, his Shanghai-based postdoc Haojie Jin, and their colleagues in Europe and China will discuss a similar resistance mechanism. Liver cancer In the journal Nature.. They found why lenvatinib, one of the few targeted drugs on the market for liver cancer, had no effect in 75-80% of patients.

The interfering substance was found to be the growth factor receptor EGFR. It is activated in the liver, as researchers have observed. cancer cell As soon as a drug called lenvatinib is given, it promotes cell division. Later, in a mouse model, researchers witnessed that tumors that were initially resistant to lenvatinib actually activated EGFR.

But they also found that it was possible to negate this resistance. cell By combining lenvatinib with another drug, gefitinib, it inhibits EGFR, similar to mice.This is an existing one medicine For example, it is already used to treat lung cancer.

600 beds for liver cancer

Liver cancer is relatively rare in the West, but certain lifestyle factors have contributed to its increased incidence. However, in Africa and Asia, liver cancer mainly due to hepatitis B and C is a major problem, and half of the world’s deaths from liver cancer occur in China. Rene Berners was a part-time chair at the alma mater of Hoazier Jin, a postdoc at Jao Thong University in Shanghai, so she was able to immediately begin human first clinical trials at the Eastern Hepatobiliary Surgery Hospital in Shanghai. ..This hospital alone has 600 beds liver cancer.

Proof-of-concept research

This phase 1 proof-of-concept study enrolled 12 patients who previously did not respond to treatment with lenvatinib and had large amounts of EGFR in their tumors. A significant reduction in tumors was observed in 4 of 12 cases. Currently, the patient cohort has been expanded to 30.After that, a large clinical study is needed before this Combination therapy It can be used in the clinic. “This study shows that it can be improved by combining existing drugs. Another advantage is that gefitinib is unpatented and affordable,” Berners said. I am.

“Pharmacists should start thinking in terms of combination therapies.”

Combination therapies are becoming increasingly important because cancers are so complex and rapidly adapted. Therefore, pharmacists need to move to an approach that involves smart combinations of drugs when developing medicines, Berners recently argued in a vision article. Hopefully, that means new therapies can reach patients faster, and promising new drugs either don’t work on their own or are less likely to fail during development because they don’t work well. ..


A library of mouse genes to find out the best liver cancer treatments


For more information:
Haojie Jin et al, EGFR activation limits the response of liver cancer to lenvatinib, Nature (2021). DOI: 10.1038 / s41586-021-03741-7

Quote: Smart combination therapy for liver cancer addresses drug resistance (July 21, 2021) July 21, 2021 https://medicalxpress.com/news/2021-07-smart-combination-therapy-liver-cancer Obtained from .html

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