{"id":23525,"date":"2019-07-24T09:04:19","date_gmt":"2019-07-24T16:04:19","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=23525"},"modified":"2024-01-30T14:53:47","modified_gmt":"2024-01-30T22:53:47","slug":"unlocking-therapies-for-hard-to-treat-lung-cancers","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/unlocking-therapies-for-hard-to-treat-lung-cancers\/","title":{"rendered":"Unlocking therapies for hard-to-treat lung cancers"},"content":{"rendered":"

LA JOLLA<\/span>\u2014<\/span>Around 85 percent of lung cancers are classified as non-small-cell lung cancers, or NSCLCs. Some patients with these cancers can be treated with targeted genetic therapies, and some benefit from immunotherapies\u2014but the vast majority of NSCLC patients have no treatment options except for chemotherapy.<\/span><\/p>\n

\"Salk
Salk researchers discovered that CREB and its partner, CRTC2, are activated in a subset of non-small-cell lung cancer tumors. The image on the top shows lung tumors (dark purple) in control-group mice compared to those that lack CRTC2 (bottom), which suggests the therapeutic potential for drugs that can interfere with CREB or CRTC2 in this subset of patients.<\/p>\n

Click here<\/a> for a high-resolution image.<\/p>\n

Credit: Salk Institute<\/figcaption><\/figure>\n

Now, <\/span>a new Salk Institute study<\/span>, published on July 24, 2019, in the journal <\/span>Science Advances<\/span><\/em><\/a>, shows that researchers could target these hard-to-treat cancers by pursuing drugs that keep a cellular \u201cswitch,\u201d called CREB, from triggering tumor growth. The study was led by <\/span>Marc <\/span>Montminy<\/span><\/a>, professor and J.W. Kieckhefer Foundation Chair at Salk, in close collaboration with Professor <\/span>\u9c81\u672c-\u8096<\/span><\/a>, director of the Salk Cancer Center and William R. Brody Chair.<\/span><\/a><\/p>\n

“A drug that blocks this switch could have therapeutic benefits for patients with non-small-cell lung cancer,\u201d says <\/span>Montminy<\/span>. \u201cThis disease has eluded efforts to identify effective treatments.\u201d<\/span><\/p>\n

Shaw adds, \u201cThere\u2019s really no good treatment, so any insight that helps this subset of patients is a major advance.\u201d<\/span><\/p>\n

Scientists have studied CREB for decades. The molecule, known as a transcription <\/span>factor<\/span> because it binds to DNA to change gene transcription, has a key role in directing which proteins a cell can make.<\/span><\/p>\n

\"(\u300a\u4e16\u754c\u4eba\u6743\u5ba3\u8a00\u300b) <\/span>Montminy<\/span> and Shaw laboratories at Salk focused on the role of CREB in patients with diabetes. Over the years, more and more research has suggested that CREB is important in cancer, but no one knew exactly how CREB affects cancer growth\u2014until recently.<\/span><\/p>\n

Laura <\/span>Rod\u00f3n<\/span>, first author and a postdoctoral researcher in the <\/span>Montminy<\/span> lab, wanted to look at which genes CREB binds to in patients with non-small-cell lung cancer to understand how CREB influences cancer\u2014and reveal potential new drug targets. To do so, the team examined how non-small-cell lung cancer cell lines grew in a mouse model, studied the tumors and correlated the results with data from tumors in patients. They discovered that CREB and its partner, CRTC2, are activated in a subset of NSCLC tumors.<\/span><\/p>\n

Normally, a tumor suppressor gene called LKB1 would block this activation\u2014but this checkpoint is gone in patients with the altered gene. In these patients, CRTC2 is abnormally activated, and stimulates genes that contribute to lung cancer. In particular, follow-up experiments showed that CRTC2 mistakenly turns on another gene called ID1, which is known to cause cancer in other tissues. <\/span><\/p>\n

\"From
From left: Marc Montminy, Laura Rod\u00f3n and Reuben Shaw.<\/p>\n

Click here<\/a> for a high-resolution image.<\/p>\n

Credit: Salk Institute<\/figcaption><\/figure>\n

\u201cIt was an exciting finding to show how CREB ultimately contributes to this deadly type of cancer,\u201d says <\/span>Rod\u00f3n<\/span>. \u201cThis gives weight to the idea that if we were able to turn off that CREB switch, we\u2019d be able to help patients.”<\/span><\/p>\n

The next step in this research is to look into potential drugs that can interfere with CREB or CRTC2 in this subset of non-small-cell lung cancer patients. Luckily, past studies that aimed to block CREB as a way of helping diabetes patients offer a suite of new possibilities for cancer treatments. Shaw says biomedical companies may have promising NSCLC drugs on hand and not even realize it.<\/span><\/p>\n

\u201cThere are a lot of interesting findings in this space,\u201d says Shaw. \u201cHopefully in the next couple years, we\u2019ll know a lot more about treating these patients.\u201d<\/span><\/p>\n

The team agrees that this study is a great example of how laboratories at Salk work together to embrace new projects.<\/span><\/p>\n

\u201cSalk encourages collaborations,\u201d says <\/span>Montminy<\/span>. \u201cThat makes it very easy to do studies like this that require people with different expertise to work together.\u201d<\/span><\/p>\n

Other authors include Robert U. <\/span>Svensson<\/span>, Ezra <\/span>Wiater<\/span>, Matthew G.H. Chun, Wen-Wei Tsai and Lillian J. Eichner of Salk.<\/span><\/p>\n

The work was funded by The National Institutes of Health (R01 DK083834, R35CA220538, P01CA120964), The Leona M. and Harry B. Helmsley Charitable Trust (grant #2012-PG-MED002), the Clayton Foundation for Medical Research, the Kieckhefer Foundation, the Tobacco-Related Disease Research Program (25FT-0006), the American Cancer Society (ACS#124183-PF-13-023-01-CSM, PF-15-037-01-DMC) and Salk (A014195).<\/span><\/p>","protected":false},"featured_media":23528,"template":"","faculty":[100,45],"disease-research":[46,164],"class_list":["post-23525","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-marc-montminy","faculty-reuben-shaw","disease-research-cancer-biology","disease-research-lung-cancer"],"acf":[],"yoast_head":"\nUnlocking therapies for hard-to-treat lung cancers - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/unlocking-therapies-for-hard-to-treat-lung-cancers\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Unlocking therapies for hard-to-treat lung cancers - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Around 85 percent of lung cancers are classified as non-small-cell lung cancers, or NSCLCs. 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