如何扼住癌症生长？ z-bo 2020-10-19 268

　　The activation of a protein called Ral can promote tumor growth and metastasis in a variety of human cancers, including pancreatic cancer, prostate cancer, lung cancer, colon cancer, and bladder cancer. Unfortunately, there are currently no drugs that can interfere with Lal's activity.

　　" A senior person said: "If you want to prevent crocodile bites, please tie the crocodile's mouth and close it tightly. I took another approach. Put a stick in the crocodile's mouth and keep the mouth open. The author is Dr. Dan Theodorsk, director of the University of Colorado Cancer Center and professor of urology and pharmacology. A new study uses several advanced computer models to detect the structure of the "inactive" al protein, and specifically studies the changes in the structure when the protein is "active." I will. The results show that when the protein is activated, the "inactivated" al has a cavity that disappears. This is the "crocodile mouth", and Theodore and others need a "stick". To find the rod they need, researchers can use a computer to put 500,000 compounds into the cavity, and 88 small candidate molecules can bind to the inactivated Ral and prevent its activation.

　　Next, the researchers tested these results on human cancer cells and used these compounds to treat the cancer cells to see which compounds can minimize Ral activation. it is. From this group of compounds, they found several compounds that can specifically reduce Ral activation in lung cancer cells (an extended reading: "Nature" draws a comprehensive molecular map of lung cancer). Further tests evaluated the ability of these compounds to slow the growth (representing metastasis) of floating human cancer cells. In this regard, the so-called RBC8 is the most successful. In order to further convert this functional molecule, the research team synthesized derivatives of RBC8, compared these derivatives with the parent molecule, and found that the compound labeled BQU57 was very effective. Next, the test targets a mouse human lung cancer cell model. Whether the cells of the animal model absorb BQU57 and make the compound a potential drug for cancer patients is an important question answered by this test. In other words, do researchers want to see if drugs that work in petri dishes also work in animals? As expected, BQU57 entered the tumor tissue several hours after administration. Not only did it invade, but the drugs slowed the growth of these tumors. The analysis results showed that BQU57 prevented the activation of Ral in the treatment of tumors.

　　Theodorescu said: “Before entering the clinic, we need to optimize these compounds, determine the toxicity of these drugs in certain animal species, and determine the best route of administration, such as oral or intravenous administration. Seen as an important first step in the development of new targeted therapies.