A new method to identify modified proteins to help the development of anticancer therapy

Researchers from the protein research center of Novo Nordisk foundation at the University of Copenhagen have developed an advanced method to identify some modified proteins that can affect the ability of DNA damage repair in cells This provides hope for the use of the latest therapies involving PARP inhibitors to improve the treatment of hereditary breast and ovarian cancer When the pharmaceutical industry develops new drugs, such as cancer treatment, it is important to understand the body's knowledge of the molecular response to the drug "The more in-depth understanding of many complex activation processes related to disease and drug treatment, the greater the possibility of developing new drugs We are now closer to targeting and treating some cancers with PARP inhibitors PARP inhibitors are a kind of drug inhibitors used in the latest cancer treatment Some tumor types rely heavily on PARP protein for self repair, and PARP inhibitors are specifically used to kill cancer cells, "said Michael Lund nielse, associate professor, protein research center, Novo Nordisk foundation, University of Copenhagen Researchers have developed an advanced method to identify proteins modified by ADP ribosylation, a biological modification that affects the ability of cells to repair DNA damage The results were published in the scientific journal Molecular Cell "The deadliest types of cancer among women are lung, breast, colon, pancreatic and ovarian PARP inhibitors seem to be an effective treatment for hereditary breast and ovarian cancer, but we know little about the details of the treatment Our new analytical method can help us to understand more about the biological function of PARP protein, so it can help us to clarify the mechanism of PARP inhibitor therapy In the long run, it will enable us to design better and more accurate PARP inhibitors, "said Michael Lund Nielsen, associate professor, protein research center, Novo Nordisk foundation, University of Copenhagen DNA repair is essential for cell health ADP ribosylation is a biochemical protein modification, which controls several important cellular processes including DNA damage repair Every day, our DNA is damaged 10 to 1 million times, so it's crucial for cells to be able to repair their DNA Healthy cells are able to repair these damage to maintain health However, some cancer cells can not repair themselves without ADP ribosylation PARP inhibitors use this to target cancer treatment It is believed that by inhibiting the ADP ribosylation of PARP protein, cancer cells can be prevented from self repairing, leading to their death Theoretically, PARP inhibitors can damage healthy cells and cancer cells, but normal cells have different survival mechanisms from cancer cells Therefore, part inhibitors seem to offer new and better cancer treatment options Treatment with PARP inhibitors PARP is a new individualized cancer therapy Targeted therapy is aimed at the inherent weakness of cancer cells Although many companies are testing them in phase 1-3 clinical trials, there is no PARP inhibitor on the market, and PARP inhibitors can only be used for experimental purposes "Our analysis method makes it possible to map the activity of PARP inhibitors, providing an opportunity to develop the best breast and ovarian cancer treatment with less side effects It can also detect whether PARP inhibition can be used in combination with chemotherapy and / or radiotherapy for other cancers In particular, radiation can have a lot of nasty side effects, but there are some signs that the best treatment can be achieved by combining radiation with PARP inhibitors, because PARP inhibitors make cancer cells more sensitive to radiation, "said Michael Lund Nielsen Using radiation and chemicals, researchers damaged DNA in cells Then they isolated the proteins modified by ADP ribosylation, identified them by mass spectrometry, determined the characteristics of the proteins and the sites of the chemical changes of ADP ribosylation.