Nat commun: epigenetic modification of DNA can promote the tolerance of breast cancer to hormone therapy

February 4, 2020 / Biovalley BIOON / -- DNA in breast cancer cells that are resistant to hormone therapy often changes epigenetics Hormone therapy is an effective therapy for ER + breast cancer, which accounts for 70% of all diagnosed breast cancer patients; reverse these epigenetics The changes may help reduce the recurrence rate of breast cancer patients Photo source: cc0 public domain recently, a research report published in the international journal Nature communications, scientists from Garvin Medical Research Institute and other institutions in Sydney found that the 3-D structure of DNA in ER + breast cancer cells that are resistant to hormone therapy may have "rewired", which can change the activation and deactivation of genes Professor Clark, the researcher, said that for the first time in this study, we have revealed a key 3-D DNA interaction, which is related to whether breast cancer is sensitive to hormone therapy Clarifying the process may help to reveal the molecular mechanism of ER + cancer avoiding hormone therapy, and hopefully help to develop new breast cancer therapy Estrogen may inadvertently promote the progress of cancer When estrogen "stops" in the cell, it will induce the growth of ER + breast cancer Hormone therapy that blocks estrogen can successfully block the growth of cancer and reduce the recurrence rate However, over time, many breast cancer will still have resistance to this therapy Treatment tolerance is a major health problem faced by cancer patients, which will lead to a third of ER + breast cancer patients receiving hormone therapy relapse within 15 years Researchers are very interested in studying the epigenetic changes of DNA, which will lead to breast cancer's tolerance to therapy, understanding the molecular mechanism behind it or helping to develop new therapies to inhibit cancer recurrence Using the technique of chromosome conformation capture (3C), researchers can reveal the pattern of DNA arrangement and interaction in three-dimensional mode At the same time, researchers can also compare the differences of ER + breast cancer cells sensitive to hormone therapy After comparative analysis, the researchers found a significant change in the way of 3-D interaction in the DNA region that controls gene activation, including the key genes that control estrogen receptor levels in cells, said researcher achinger kawecka The researchers point out that this 3-D rewiring pattern may occur in the methylated DNA region, and this epigenetic change may be directly related to the tolerance of cancer cells to hormone therapy DNA methylation in key regulatory regions may be able to explain the rearrangement of DNA 3-D structure, which may induce cancer cells to have tolerance to hormone therapy, so as to better avoid the effect of therapy Cancer cells will always try their best to avoid treatment It only needs one cell to evolve a different way to bypass drugs to induce cancer recurrence In this study, the researchers have revealed how epigenome changes affect the behavior of cancer cells In the next step, the researchers will continue to conduct in-depth research to clarify whether the current drugs for other cancers (including lung cancer and colorectal cancer) can be used to reverse epigenetics Finally, researcher Clark said that once ER + breast cancer patients have tolerance to hormone therapy, it will be difficult to treat them We hope that the results of this study can help to develop new combined therapy to improve the survival period and quality of life of breast cancer patients Original sources: achinger kawecka, J., Valdes mora, F., Lu, P et al Epigenetic reprogramming at estrogen receiver binding sites alterers 3D chromatin landscape in endocrine resistant burst cancer NAT Commission 11, 320 (2020) Doi: 10.1038/s41467-019-14098-x