Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases

摘要: Healthy cells in the human body can become cancerous if they gain genetic mutations that allow them to rapidly grow and divide. Some types of cancer respond better drug treatments than others tumors often develop resistance a particular treatment after while. Because this, researchers are always searching for new molecules into anticancer drugs. Recently, team identified some small could inactivate two closely related proteins called CDK8 CDK19. is essential WNT signaling pathway – which enables communicate with one another has been extensively studied various cancers. Previous studies indicate this protein either promote or inhibit growth tumors, depending on type stage cancer. Furthermore, regulates molecular switch “super-enhancer”, controls activity many genes. In contrast, role CDK19 was not as well understood. Here Clarke, Ortiz-Ruiz et al. investigated whether different classes target (referred “prototype CDK8/19 drugs”) cancers, have any harmful side effects healthy cells. For experiments, were implanted mice. Treating these mice prototype drugs inhibited slowed colorectal tumors. A blood acute myeloid leukaemia particularly sensitive However, also observed altered genes roles tissues such immune, bone stem Further experiments grown laboratory confirmed adverse intestinal marrow trigger changes immune These concerning evident when tested rats dogs. there suitable range doses therapeutic benefits outweigh toxic effects. conclude clinical development will be extremely challenging their would currently use treatments. describe important probes research study exactly how regulate gene both