Cell: Combination therapy makes tumor immunotherapy "like a tiger"
December 04, 2017 Source: Bio-Exploration
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Researchers at the Johns Hopkins Kimmel Cancer Center have found that the combination of several epigenetic treatments for non-small cell lung cancer allows them to better respond to immunotherapy in human cancer cell lines and The anti-tumor response is achieved in mice.
On November 30, 2017, the study, published in Cell, will be called "5-azacytidine" demethylation, and inhibits cell replication associated with cancer development. It is used in combination with the mitotic "HDACis (histone deacetylase inhibitor)" to stimulate the action of tumor suppressor genes.
This combination therapy triggers a chemical cascade that increases the "combat power" of immune cells on the tumor and reduces the role of the oncogene MYC. Based on these findings, the researchers will implement this method in clinical trials in patients with advanced non-small cell lung cancer.
â–‹ 1. Molecular mechanism of combination therapy
In a series of experiments, the researchers studied 5-azacytidine-binding histone deacetylase inhibitors entinostat, mocetinostat or givinostat (the three inhibitors are also anticancer drugs) in human cancer cells and non-small Role in a mouse model of cellular lung cancer.
Studies have found that related treatments can alter the tumor microenvironment. In tumor cell lines, 5-azacytidine inhibits the oncogene MYC, resulting in down-regulation of the entire MYC signaling pathway. The added histone deacetylase inhibitor further invalidates the MYC gene, and the effect of the drug together prevents the proliferation of cancer cells, and at the same time attracts more immune system T cells to reach the tumor surface and activate these cells to recognize the tumor. .
â–‹ 2, combined with drugs can control tumors
In the mouse model, the most intense response was observed when 5-azacytidine plus givinostat was used. In a mouse model of mutated non-small cell lung cancer, the drug was administered in combination for three months to prevent the benign tumor from becoming a cancer, and the overall appearance of the benign tumor of the lung was reduced by 60%. In contrast, a large number of cancerous lesions appeared in the lungs of a group of mice with the same lung cancer type who received control treatment.
In a second mouse model established with aggressive non-small cell lung cancer, alternating treatment with 5-azacytidine and givinostat and 5-azacytidine with mocetinostat not only reduced the original tumor growth, the primary The incidence of metastatic tumor metastasis was also significantly reduced.
â–‹ 3, combined use of drugs to promote the increase of tumor immune recognition
Corresponding author Stephen B. Baylin said: "The development of treatments for patients with lung cancer is an important medical need. Although immunological checkpoint therapy is a big step forward, less than half of lung cancer patients benefit. â€
He pointed out that "in our study, even before the use of immunological checkpoint inhibitors, the two epigenetic therapies work very well. In the animal model of lung cancer, these two drugs can prevent cancer. It can also attenuate the aggressiveness of cancer. In both cases, an important component of the outcome is the increase in tumor immune recognition."
Reference materials:
1) Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating Lung Cancer
2)Two-drug combination may boost immunotherapy responses in lung cancer patients
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