Research has found that a small molecule drug can prevent cancer cells from developing drug resistance
Last Update: 2020-06-19
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However, cancer cells are very "smart", relying on "imperfect" DNA repair mechanism to avoid this pursuit, and thus produce resistance to chemotherapy drugsThis is also the main cause of 90% cancer recurrence and related diseases death< br / > however, in the latest "cell" magazine, a study on new cancer chemotherapy drugs jointly published by MIT and Duke University has found a new small molecule drug that can block the drug resistance pathway of cancer cellsThe combination of this small molecule drug and cisplatin can enhance its killing ability to cancer cells and prevent the new mutation of drug resistance of cancer cells< br / > doi: < br / > the "imperfect" repair leads to the generation of drug resistance < br / > Graham walker, senior author of the study and professor of biological research of American Cancer Association of Massachusetts Institute of technology, found in previous studies that healthy cells can accurately repair DNA damage in cells after damageHowever, when cells become cancer cells, they can no longer rely on this normal repair systemInstead, they use TLS (Synthesis of cross damaged DNA) for repairspecifically, normal cells can produce normal polymerases to repair cells accurately, but when cancer cells use special TLS DNA polymerases to repair cells, they can not repair cells completely and accurately< br / > it is this "imperfect" DNA replication process that mostly leads to mutations in cancer cells, and new mutations make cancer cells have to have resistance to previous chemotherapy drugs, thus affecting the therapeutic effect on cancer cells< br / > one of the "new killing weapons" < br / > in this study, researchers found that TSL DNA polymerase Rev1 is one of the key enzymes needed in the process of TSL synthesis and repairIts main function is to collect the second TLS DNA polymeraseResearchers have also been looking for ways to disrupt this "Recruitment" activity, hoping to disrupt the repair process of this cancer cell< br / > in the past 10 years, it has been found that interfering with transmembrane synthesis may be an effective way to destroy this "Recruitment"Therefore, researchers have screened about 10000 potential drug compounds, hoping to find small molecule drugs that play a role of "interference"< br / > researchers have been reluctant to look forward to this search, because the interaction between Rev1 and rev7 in the second TLS DNA polymerase is considered to be "unstoppable", and this reaction takes place in a very shallow bag of Rev1, with only a few features that are easy to be recognized and locked by drugshttps ：// doi.org/101016 / J.Cell2019.05.028 < br / > however, it is exciting that they found such a molecule jh-re-06, which can combine with two molecules of Rev1, one at each end, and combine them to form a compound called dimerMoreover, Rev1 in such a dimer form cannot bind to Rev3 / rev7 TLS DNA polymerase, thus preventing TLS from occurring< br / > the structure of the complex containing Rev1 and jh-re-06Two copies of Rev1 protein are shown in dark blue and light blue, while the small molecule jh-re-06 sandwiched between them is shown in bright pinkPhoto source: Professor Pei Zhou < br / > found that nimrat Chatterjee, a postdoctoral of MIT, said excitedly: "this new type of transmembrane synthesis inhibitor can target the mutagenic ability of drug resistance of cancer cells, and provide a new treatment idea for solving cancer recurrence." < br / > in order to further verify the efficacy of jh-re-06, Dr Chatterjee carried out experiments on mice suffering from human melanomaIt was found that the tumor reduction degree of jh-re-06 combined with cisplatin (CDDP) was far greater than that of cisplatin alone, At the same time, it was found that the ability of combination therapy to reduce the new mutation of cancer cells was far greater than that of cisplatin alone< br / > to achieve more accurate and effective cancer treatment, researchers are redoubling their efforts to develop the new drugCurrently, Professor Pei Zhou and his team are working in the Duke University Laboratory to develop variants of the compound that can be used for human patient testingProfessor Walker and Professor Hemann are also further studying the mechanism of action of the drug to determine the best use of the drug< br / > reference materials: < br / >  a small molecule targeting chemical transformation synthesis improves chemotherapy
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