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A study by the Paul Scherrer Institute in Switzerland, in collaboration with Roche, a well-known multinational pharmaceutical company based in Switzerland, is an important step in the resolution of the malignant metastasis of some common cancers. The research team focused on the lymphatic metastasis process of cancer cells, deciphering the structure of a key signaling molecule for the first time, and based on this, screened out drug candidates for this target. This achievement was recently published in the leading academic journal Cell.

The lymphatic system is an important way for cancer cells to spread. Like the blood system, the lymphatic system runs through the body, and the lymphatics connect the lymph nodes to each other. Cancer cells migrate therein and are associated with signals received on the cell surface.

Under normal circumstances, lymphocytes in the human immune system will continue to flow to the lymph nodes through the chemokine receptor-7 (referred to as CCR7), enter the lymph system, spread in the body, and eventually form metastases in other tissues. Because of this, scientists at PSI and Roche use CCR7 as a potential target for interfering with lymphatic proliferation of cancer cells. "Finding the right molecule prevents the signal protein from binding to the receptor and prevents the signal from being passed on to the cancer cells," said co-author Dr. Steffen Brünle.

However, so far, there are only a handful of small molecule drugs targeting chemokine receptors in the market, and clinical trials of related drugs often fail due to poor effectiveness and selectivity. In order to overcome these obstacles, scientists thought of gaining insights from the molecular structure, and first analyzed the 3D structure of the CCR7 protein

"The first difficulty encountered was making proteins, making them detectable by X-ray crystallography," said Dr. Jörg Standfuss, one of the co-leaders. To speed up the research process, Roche has developed a new protein modification technology module that uses a "crystal chaperone" to determine the structure of the human CCR7 protein.

The initial results are pleasing. "Our experiments show that artificial molecules bind to receptors in cells, and the intracellular chain reaction that causes cell migration cannot be turned on," said Dr. Brünle.

To researchers' surprise, Navarixin, an active molecule in the screening results, has entered phase 2 clinical trials as a potential anti-metastatic drug for colorectal cancer and some other aggressive cancers. This result indicates that this is a multi-target antagonist, which is likely to help when single-target therapy is resistant.

We expect scientists to follow up all the research smoothly and bring new drugs to block the malignant metastasis of cancer cells as soon as possible, so that more patients will never be afraid of cancer.