Stop malignant tumor metastasis Scientists find new targets to crack cancer killers
Last Update: 2020-06-17
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Ninety per cent of cancer patients lose their lives as a result of malignant metastasisIn order to improve the survival rate of cancer patients, it is undoubtedly important to inhibit the metastasis of cancer cellsThis is also a challenge that many researchers are trying to challengea study by the Paul Scherrer Institute in Switzerland in collaboration with Roche, a well-known Swiss-based multinational drugmaker, is an important step in cracking the malignant metastasis of some common cancersThe team focused on the lymphatic metastasis process of cancer cells, deciphering for the first time the structure of a key signaling molecule and, on that basis, screening the candidate drug molecules for this targetThe results were recently published in the leading academic journal Celllymphatic system is an important way for cancer cells to spreadLike the blood system, the lymphatic system runs through the body, and the lymphatic nodes connect to each otherIn which cancer cells migrate, it is related to the signals received on the cell surfacesignal transmission is very important in the biological world, between individuals need to transmit signals, and cells also need to transmit signals between themIn vertebrates, chemofactors are a kind of signaling protein commonly used in cellsMore than 40 different chemo factors, each binding only to a specific chemochemical receptor on the cell surfaceAfter binding, the cells respond specifically to the signalchemofactor receptor-7 (CCR7) is a receptor that controls cell motionWhen they bind to the appropriate signaling protein outside the cell, a chain reaction occurs within the cell, causing the cell to move in the direction of the highest concentration of the signal proteinCells follow chemofactors, just as hounds follow the odor trackingnormally, lymphocytes in the body's immune system continue to flow to the lymph nodes with THE help of CCR7 But crafty cancer cells can use CCR7 to meet their expansion needs Signaling proteins lead them away from the original tumor, enter the lymphatic system, spread in the body, and eventually form metastatic tumors in other tissues cancer cells use CCR7 to the lymph nodes transfer (Photo: References) because of this, PSI and Roche scientists have used CCR7 as a potential target for interfering with the spread of cancer cells' lymphatic "Finding the right molecule prevents the signal protein from binding to the receptor and does not allow the signal to pass on to the cancer cells "Together, Dr Steffen Br?nle said , however, so far, there are a handful of small molecular drugs on the market that target the receptors of chemators, and clinical trials of related drugs have often failed because of poor efficacy and selectivity To break through these barriers, the scientists came up with insights from molecular structures, first analyzing the 3D structure of the CCR7 protein " the first difficulty was making proteins that could be detected with X-ray crystallography One of the co-leaders, Dr J?rg Standfuss, introduced To speed up the research process, Roche has developed a new protein modification technology module that uses "crystalline mates" to determine the structure of the human CCR7 protein CCR7 receptor and intracellular antagonist Cmp2105 (Photo Source: References) the precise structure of the receptor opens up a new way for the design of small molecule drugs The team began searching for active substances that could be specifically binding to the ligand and CCR7 cell site specificity Using computer simulations of Roche's 2.3 million compounds, scientists screened nearly 300 compounds based on 3D shape similarity, and then identified five compounds as candidates to further develop potential cancer drugs by measuring thermal stability preliminary results are encouraging "Our experiments have shown that artificial molecules bind to receptors within cells, causing intracellular chain reactions that cause cell migration to be unable to turn on "Dr Br?nle introduced five small molecular ligands (pictured: References) that the screening results of one of the active molecules Navarixin have entered Phase 2 clinical trials as a potential anti-metastatic drug for colorectal cancer and other invasive cancers It used to be thought to bind to another receptor, inhibiting other functions of cancer cells This result suggests that this is a multi-target antagonist that is likely to help when single-target therapy is resistant References: K Jaeger et al., (2019) Rq basis for allosteric ligand recognition in the human CC Chemokine eth Cell DOI: 10.1016/j.cell.2019.07.028 Retrieved Aug 25, 2019, from original title: "Cells": Stopping Malignant Tumor Metastasis, Scientists Find New Targets to Crack Cancer Killers
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