Epigenetic study reveals a new combination therapy for invasive cancer

Photo source: Nature Genetics < br / > modern whole genome screening technology makes it possible to generate mutant cell populations, and one gene in each cell is destroyedBrd4 reporting cells enable Stefan Kubicek to select precisely those cells that exhibit Brd4 inhibition from these cell populations in CeMM's laboratoryNext generation sequencing is then used to determine which genes are turned offKubicek said: "we thought we could find a classic epigenetic factor, so we were even more surprised that the most suitable gene was mthfd1"This enzyme is involved in folate metabolism, which has never been found to be related to Brd4 beforeIn addition, mthfd1 is mainly located in the cytoplasm, while Brd4 is located in the nucleus< br / > these coincidences provide another piece of puzzle for the first author Sara sdelci, confirming the research resultsAt a meeting, she met Philip rathert from the imp Johannes Zuber lab, who is also working on Brd4Sara sdelci said: "data from Philipp rathert show that mthfd1 is also physically integrated with Brd4"In subsequent experiments, she found that a small part of the mthfd1 protein found in the nucleus interacted with Brd4This interaction absorbs mthfd1 into DNA, where the enzyme is involved in gene regulationThe study of < br / > Sara sdelci has clinical significance for Brd4 dependent tumorsThis includes tumors that carry genes that cause Brd4 overexpression, as well as many other cancers in which Brd4 promotes cell growth through its gene regulatory functionTherefore, pharmaceutical companies have developed Brd4 inhibitors with high activity, which are currently being tested in clinical trials< br / > in clinical oncology, due to the development of drug resistance, single drug treatment of single chemical agent is rarely successfulThe discovery of the interaction between Brd4 and mthfd1 in folate metabolism provides a new way for the combined treatment of tumor and the treatment of invasive tumorAnti folate is a kind of substance which can inhibit folate circulation It has been used in cancer treatment and rheumatoid arthritis for more than 70 years New research shows that anti folate can be used in combination with Brd4 inhibitors to fight tumor more effectively The results also help to classify patients to ensure treatment success Stefan Kubicek said: "according to our research results, in the best case, we can also select patients who respond particularly well to Brd4 inhibitors according to their folate levels and genes "< br / > reference materials: < br / > Sara sdelci et al, mthfd1 interaction with Brd4 links follow methodology to transactional regulation, Nature Genetics (2019) Doi: 10.1038/s41588-019-0413-z