Nature Sub-Journal: Brown University Study: Medication may improve the effectiveness of cancer immunotherapy.

Introduction: immunotherapy is a treatment that uses the body's own immune system to identify, attack and kill tumor cells. Although it has brought hope to people all over the world, it has failed in many cancer patients.recently, researchers from Brown University in the United States found that drugs that block tumor promoting protein MDM2 can enhance the effectiveness of immunotherapy.tumor immunotherapy aims to activate the human immune system and kill cancer cells and tumor tissues by autoimmune function.this has completely changed the traditional cancer treatment methods and produced significant reactions to a variety of previously refractory tumors.however, drug resistance in patients receiving immunotherapy remains a major challenge.in addition to primary drug resistance, another challenge is the phenomenon of over progression of disease (HPD), i.e., accelerated tumor growth in patients receiving immunotherapy.recently, researchers from Brown University in the United States have found that drugs that block tumor promoting protein MDM2 can increase the efficacy of immunotherapy.the study was led by Dr. wafik El deiry, Associate Dean, Department of oncology, Brown University, and published online in cell death discovery, a sub Journal of nature.titled "amg-232 senses high MDM2 expressing tumor cells to T-cell-mediated killing", Professor El deiry said: "immunotherapy is one of the biggest breakthroughs in biomedical and medical fields in the past 20 years, but it also has limitations."some patients have tumors that initially respond to immunotherapy and then recur.however, some patients may experience pseudo progression, i.e. the tumor begins to grow again before it gradually shrinks.there are also patients (5% to 29% of all patients) who experience over progression, which means that immunotherapy actually worsens their tumor growth.many previous studies have found that when MDM2 gene is amplified (which means there are too many copies of the gene in cells), or when MDM2 protein is overexpressed due to improper gene regulation, tumor cells tend to grow faster and are more resistant to immunotherapy.researchers are still studying why this accelerated growth and resistance phenomenon occurs, but studies have shown that MDM2 can help tumor growth and escape the immune system through a variety of mechanisms.for example, MDM2 seems to inactivate tumor suppressor gene p53 and prevent immune cells from killing tumor cells, and it is also associated with increased levels of a pro tumor inflammatory protein, interleukin-6 (IL-6).the high expression of MDM2 contributes to immune escape. Therefore, El deiry hopes to block MDM2 through gene silencing or amg-232, which inhibits MDM2, so as to enhance the effect of immunotherapy.in this study, they used amg-232 to treat ovarian cancer cell lines with MDM2 overexpression. experimental data show that amg-232 can make immune cells kill tumor cells more effectively and reduce the level of IL-6. these results suggest that MDM2 inhibitors can be combined with immunotherapy to improve their efficacy. targeting MDM2 by amg-232 makes MDM2 overexpression tumor cells sensitive to T-cell-mediated killing. For this finding, El deiry hopes that this study will be able to conduct clinical trials so that the research team can further evaluate the safety and efficacy of this new therapy. since MDM2 amplification and overexpression are associated with a variety of cancers, he believes that amg-232 (or similar drugs, including drugs that block MDM2 and its related protein mdmx) can be widely used, and even benefit immunotherapy patients with normal MDM2 levels. El deiry said: "we think this may be a good treatment for patients with over progression of cancer, but I would like to say that our results show that targeted MDM2 combined with immunotherapy can work well even if MDM2 is not amplified or overexpressed. it takes advantage of the vulnerability within the tumor to help immunotherapy work better. "the study was conducted after the establishment of Brown University Cancer Center, where El deiry was the first director. based on Brown University's increasing emphasis on translational science, the center is committed to understanding how cancer develops, grows and metastasizes to developing new therapies for patients in a personalized way to meet their needs from risk to survival. reference: [1] Ilyas Sahin et al, amg-232 senses high MDM2 expressing tumor cells to T-cell-mediated killing, Cell death discovery (2020). Doi: 10.1038/s41420-020-0292-1 [2] [3] recommended reading: fighting the epidemic situation, translational medicine network content team series report: [cell] major progress: Chinese scientists reveal the complete proteome map of lung adenocarcinoma for the first time [invitation] 2020 Qidong Greenland Health Technology Industrial Park Investment Fair and in vitro diagnosis Summit Forum, we sincerely invite you to participate! 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