{"id":11034,"date":"2016-09-19T00:00:46","date_gmt":"2016-09-19T07:00:46","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&#038;p=11034"},"modified":"2024-01-30T15:28:02","modified_gmt":"2024-01-30T23:28:02","slug":"targeting-fat-treat-cancer","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/de\/news-release\/targeting-fat-treat-cancer\/","title":{"rendered":"Targeting fat to treat cancer"},"content":{"rendered":"<p>LA JOLLA\u2014Fat isn\u2019t just something we eat: it may also lie at the heart of a new approach to treating cancer.<\/p>\n<div class=\"row\" style=\"\"><div class=\"col-md-8 col-md-push-2\"><div class=\"video-anchor\" id=\"video-TiDGhJPnMw8\"><\/div><div class=\"embed-responsive embed-responsive-16by9\"> <iframe class=\"embed-responsive-item\" src=\"\/\/www.youtube.com\/embed\/TiDGhJPnMw8?rel=0\" webkitallowfullscreen mozallowfullscreen allowfullscreen><\/iframe><\/div><!-- .embed-responsive --><\/div><!-- .col-md-*size --><\/div><!-- .\/row -->\n<p>Cells create their own fat molecules to build their plasma membranes and other critical structures. Now, researchers at the Salk Institute, along with academic and industry collaborators, have found a way to obstruct this instrumental process to stifle cancer\u2019s growth, detailed September 19, 2016 in <a href=\"http:\/\/www.nature.com\/nm\/journal\/vaop\/ncurrent\/full\/nm.4181.html\" target=\"_blank\" rel=\"noopener\"><em>Nature Medicine<\/em><\/a>. Like halting the delivery of supplies to a construction site, the approach stalls the molecular building blocks cancer needs to grow.<\/p>\n<p>\u201cCancer cells rewire their metabolism to support their rapid division,\u201d says Salk Professor <a href=\"https:\/\/www.salk.edu\/de\/scientist\/reuben-shaw\/\">Reuben Shaw<\/a>, whose lab has made significant progress in establishing the ties between cancer and metabolic processes. \u201cBecause cancer cells are more reliant on lipid synthesis activity than normal cells, we thought there might be subsets of cancers sensitive to a drug that could interrupt this vital metabolic process.\u201d<\/p>\n<p>Researchers had previously hypothesized that interrupting cells\u2019 lipid assembly line could disable <a href=\"https:\/\/www.salk.edu\/de\/science\/research\/cancer-biology\/\">Krebs<\/a>, but it was only recently that they were able to disrupt the process and test this theory. Shaw\u2019s team partnered with a Boston-based biotech, Nimbus Therapeutics, which discovers and develops small molecules in the hopes of treating a variety of diseases, who were developing a molecule to shut off a critical player in lipid synthesis, an enzyme called acetyl-CoA carboxylase, or ACC.<\/p>\n<figure id=\"attachment_11042\"  class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"176\" class=\"img-responsive wp-image-11042 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/OilRedO-ACC-Control-KO-458x176.jpg\" alt=\"oilredo-acc-control-ko\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/OilRedO-ACC-Control-KO-458x176.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/OilRedO-ACC-Control-KO-300x115.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/OilRedO-ACC-Control-KO-147x56.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/OilRedO-ACC-Control-KO-585x225.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/OilRedO-ACC-Control-KO-553x212.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/OilRedO-ACC-Control-KO.jpg 659w\" sizes=\"auto, (max-width: 458px) 100vw, 458px\" \/><figcaption class=\"wp-caption-text\">Salk Institute researchers and collaborators develop novel cancer treatment that halts fat synthesis in cells. Placebo-treated cells (left) have far more lipid (red) production compared to ND-646 treated cells (right). <\/p>\n<p><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/OilRedO-ACC-Control-KO.jpg\" target=\"_blank\" rel=\"noopener\">Klicken Sie hier<\/a> f\u00fcr ein hochaufl\u00f6sendes Bild.<\/p>\n<p>Kredit: Salk Institut<\/figcaption><\/figure>\n<p>\u201cThis confirms that shutting down endogenous lipid synthesis could be beneficial in some cancers and that inhibitors of the ACC enzyme represent a feasible way to do it,\u201d said Rosana Kapeller, Chief Scientific Officer at Nimbus Therapeutics and a co-author of the paper. \u201cWe\u2019ve taken a novel computational chemistry approach to designing high-potency allosteric inhibitors of this difficult enzyme, and we are very encouraged by the results.\u201d<\/p>\n<p>In multiple and extensive large-scale tests in both animal models of cancer and in transplanted human lung cancer cells, the results of the novel ACC inhibitor, dubbed ND-646, were far more promising than expected: tumor mass shrank by roughly two-thirds compared to untreated animals. And when the researchers paired ND-646 with one of the common treatments for non-small lung cancer called carboplatin, the anti-tumor response was even greater: a dramatic 87 percent of tumors were suppressed, compared to 50 percent with the standard treatment of carboplatin alone.<\/p>\n<p>This combination of carboplatin (which damages DNA, a problem for rapidly dividing cells) and ND-646 (knocking out ACC and halting lipid synthesis) didn\u2019t seem to impair normal cells even as it dramatically slowed cancer growth.<\/p>\n<p>\u201cWe found surprisingly well-tolerated dosing with some of these novel ACC inhibitors that have broad bioavailability and should not be far away from what would be needed to initiate clinical trials,\u201d says first author Robert Svensson, a Salk research associate.<\/p>\n<figure id=\"attachment_11038\"  class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"305\" class=\"img-responsive wp-image-11038 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/IMG_4818-458x305.jpg\" alt=\"img_4818\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/IMG_4818-458x305.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/IMG_4818-300x200.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/IMG_4818-768x512.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/IMG_4818-1024x683.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/IMG_4818-147x98.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/IMG_4818-585x390.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/IMG_4818-553x369.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/IMG_4818-750x500.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/IMG_4818-945x630.jpg 945w\" sizes=\"auto, (max-width: 458px) 100vw, 458px\" \/><figcaption class=\"wp-caption-text\">From left: Martina Wallace, Amanda Hutchins, Lilliana Vera, Portia S. Lombardo, Jeanine L. Van Nostrand, Sonja N. Brun, Alan Saghatelian, Lillian J. Eichner, Matthew J. Kolar, Robert U. Svensson, Christian M. Metallo and Reuben J. Shaw<\/p>\n<p><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/09\/IMG_4818.jpg\" target=\"_blank\" rel=\"noopener\">Klicken Sie hier<\/a> f\u00fcr ein hochaufl\u00f6sendes Bild.<\/p>\n<p>Kredit: Salk Institut<\/figcaption><\/figure>\n<p>\u201cThis is the first time anyone has shown that this enzyme, ACC, is required for the growth of tumors and this represents compelling data validating the concept of being able to target fat synthesis as a novel anticancer approach,\u201d adds Shaw, who is the holder of the William R. Brody Chair. \u201cThe implications are that we have a very promising drug for clinical trials for subtypes of lung cancer as well as liver and other types of cancer. This represents a new weapon in the arsenal to fight cancer.\u201d<\/p>\n<p>Other authors on the work include: Lillian J. Eichner, Matthew J. Kolar, Sonja N. Brun, Portia S. Lombardo, Jeanine L. Van Nostrand, Amanda Hutchins, Lilliana Vera, Laurie Gerken, and Alan Saghatelian of the Salk Institute; Jeremy Greenwood and Sathesh Bhat of Schr\u00f6dinger; Geraldine Harriman, William F. Westlin and H. James Harwood Jr., of Nimbus Therapeutics; and Seth J. Parker, Martina Wallace, and Christian M. Metallo of the University of California, San Diego.<\/p>\n<p>The work was funded by: <a href=\"https:\/\/www.nih.gov\/\" target=\"_blank\" rel=\"noopener\">Nationale Gesundheitsinstitute <\/a>(R01CA172229, P01CA120964), the <a href=\"http:\/\/www.waxmancancer.org\/\" target=\"_blank\" rel=\"noopener\">Samuel Waxman Krebsforschungsstiftung<\/a>, The <a href=\"http:\/\/helmsleytrust.org\/\" target=\"_blank\" rel=\"noopener\">Die gemeinn\u00fctzige Stiftung von Leona M. und Harry B. Helmsley<\/a> und die <a href=\"http:\/\/www.defense.gov\/\" target=\"_blank\" rel=\"noopener\">Department of Defense<\/a>.<\/p>\n<p>About ND-646: Gilead Sciences, Inc. acquired Nimbus\u2019 ACC inhibitor program in May 2016, including ND-646 and other ACC inhibitors for the treatment of non-alcoholic steatohepatitis (NASH) and for the potential treatment of hepatocellular carcinoma (HCC) and other diseases. For more information, please visit <a href=\"http:\/\/www.NimbusTx.com\" target=\"_blank\" rel=\"noopener\">www.NimbusTx.com<\/a>.<\/p>","protected":false},"featured_media":11035,"template":"","faculty":[45],"disease-research":[46,164],"class_list":["post-11034","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-reuben-shaw","disease-research-cancer-biology","disease-research-lung-cancer"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Targeting fat to treat cancer - 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\/de\/news-release\/targeting-fat-treat-cancer\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Targeting fat to treat cancer - 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