Smart combination therapy for liver cancer tackles drug resistance

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

Finding alternative pathways for cancer cells

Gradually, the anticancer agent suppresses the effects of DNA errors – called targeted therapies – on cancer cells. Unfortunately, cancer cells are often resistant or become resistant to these drugs. They then continue to divide via alternate intracellular signaling pathways. Molecular cancer researcher Rene Bernards 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 pathways in 2012. He wanted to know why some drugs do nothing for certain hard-to-treat forms of colon cancer, while they work well for melanoma with the exact same mutation. DNA. He then realized that the combination of the first and second drugs would block this path. It was an innovative discovery that led to a combination of longevity. 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.

Combination therapy for liver cancer overcomes resistance

This week, Bernards, his Shanghai-based postdoctoral fellow Haojie Jin, and their colleagues in Europe and China will discuss a similar resistance mechanism. Liver cancer In the review Nature.. They found out 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 medicine called lenvatinib is given, it promotes cell division. Later, in a mouse model, researchers found that tumors initially resistant to lenvatinib actually activated EGFR.

But they also discovered that it was possible to deny this resistance. cellular By combining lenvatinib with another drug, gefitinib, it inhibits EGFR, like in mice. This is an existing drug. 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 all liver cancer deaths worldwide occur in China. Rene Berners was part-time president of the alma mater of Hoazier Jin, a post-doctoral fellow at Jao Thong University in Shanghai, so she was able to immediately start the first human clinical trials at the Eastern Hepatobiliary Surgery Hospital. from Shanghai. ..This hospital alone has 600 beds for liver cancer.

Search for proof of concept

This Phase 1 proof of concept study included 12 patients who had previously failed to respond to lenvatinib treatment and who 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 can be used clinically. “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 gaining more and more importance due to the complexity and rapid adaptation of cancers. Therefore, pharmacists must take an approach that involves smart combinations of drugs when developing drugs, Berners recently argued in an article on vision. Hopefully this means that 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. ..