Lung cancer immunotherapy, this type of blood test predicts more effective
March 19, 2018 Source: WuXi PharmaTech
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)];Immunotherapy is a major breakthrough in the field of cancer treatment. Immune checkpoint inhibitors that are already on the market produce excellent results in a variety of cancer patients, including lung cancer, but not all cancer patients respond to these therapies. Researchers at the Walter and Eliza Hall Institute of Medical Research in Australia have found that a combination of genetic mutations is responsible for the development of particularly aggressive lung cancer, and their findings suggest Immunological checkpoint inhibitors can produce good results for this type of lung cancer. The study was published in the journal Cell Metabolism.
Lung cancer is the leading cause of death from cancer in the world. Lung adenocarcinoma (ADC) belongs to non-small cell lung cancer and is the most common type of lung cancer. In lung adenocarcinoma, more than 20% of tumors show genetic variation in the KEAP1/NRF2 signaling pathway. These tumors are very aggressive, resistant to both radiotherapy and chemotherapy, and have a poor prognosis. Therefore, patients are in urgent need of new treatments for them.
Australian researchers studied KEAP1/NRF2 and PI3K signaling pathways in a transgenic mouse model. They found that simultaneous activation of KEAP1/NRF2 and PI3K signaling pathways led to the development of lung adenocarcinoma in mice. More importantly, studies of the microenvironment of the lungs carrying these tumors have shown that tumor cells can increase the expression of PD-L1 protein, while the level of PD-1 receptor protein on the surface of CD8-positive T lymphocytes in the lungs is significantly elevated. . These indications indicate that this tumor is capable of producing an immunosuppressive microenvironment in the lungs, and also means that immune checkpoint blocking therapy against PD-1 or CTLA-4 may be effective against them.
To validate the effectiveness of immunological checkpoint blockade therapy, the researchers treated mice bearing this tumor with anti-PD-1 and anti-CTLA-4 combination therapy. Experimental results show that immunological checkpoint blockade therapy can significantly reduce tumor volume.
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At the same time, studies using metabolite levels in mouse plasma using liquid and gas-phase mass spectrometry indicate that sustained activation of the KEAP1/NRF2 signaling pathway causes significant changes in the glucose metabolism pattern in mice, resulting in multiple glucose metabolism in plasma. Changes in levels of matter and nucleotides. The changing nature of these metabolites in plasma can help develop a blood test.
“We hope that this blood test will help identify cancer patients who may respond to immunotherapy. At the same time, it may become a simple, non-invasive method of detecting early lung cancer,†senior author of the article, Walter and Eliza Hall. Dr. Kate Sutherland of the Institute of Medicine said.
Next, the researchers will analyze human samples to see if the results found in the mouse model are consistent with data obtained in human lung adenocarcinoma patients.
Reference materials:
[1] Cancer 'signature' first step toward blood test for patients
[2] Synergy between the KEAP1/NRF2 and PI3K Pathways Drives Non-Small-Cell Lung Cancer with an Altered Immune Microenvironment
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