{"id":2514,"date":"2014-11-19T00:00:00","date_gmt":"2014-11-19T08:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/salk-scientists-deliver-a-promising-one-two-punch-for-lung-cancer\/"},"modified":"2014-11-19T00:00:00","modified_gmt":"2014-11-19T08:00:00","slug":"salk-scientists-deliver-a-promising-one-two-punch-for-lung-cancer","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/salk-scientists-deliver-a-promising-one-two-punch-for-lung-cancer\/","title":{"rendered":"Salk scientists deliver a promising one-two punch for lung cancer"},"content":{"rendered":"<p>LA JOLLA\u2013Scientists at the Salk Institute have discovered a powerful one-two punch for countering a common genetic mutation that often leads to drug-resistant <a href=\"https:\/\/www.salk.edu\/es\/ra\/cancer.html\/\">cancers<\/a>. The dual-drug therapy\u2013with analogs already in use for other diseases\u2013doubled the survival rate of mice with lung cancer and halted cancer in pancreatic cells.\n<\/p>\n<p>\nLung cancer, which affects nonsmokers as well as smokers, is the most common cancer worldwide, causing <a href=\"http:\/\/www.who.int\/mediacentre\/factsheets\/fs297\/en\/\" target=\"_blank\">1.6 million deaths<\/a> a year, far more than pancreatic, breast and colon cancer combined. About 30 percent of the most common type of lung cancer (non-small) contains a mutation in a gene called KRAS. This mutation can also lead to hard-to-treat cancer in the pancreas, thyroid and colon.\n<\/p>\n<p><iframe src=\"\/\/www.youtube.com\/embed\/6Ow10qe6bw8\" frameborder=\"0\" allowfullscreen><\/iframe><\/p>\n<p>\n\u201cThere really have been no effective treatments to target the KRAS mutation so far,\u201d says <a href=\"https:\/\/www.salk.edu\/es\/faculty\/verma.html\/\">Inder Verma<\/a>, a professor in the <a href=\"https:\/\/www.salk.edu\/es\/faculty\/laboratory_of_genetics.html\/\">Laboratorio de Gen\u00e9tica<\/a> and American Cancer Society Professor of Molecular Biology. \u201cWe found a drug combination that successfully targets KRAS and stops tumor growth in the mouse model.\u201d\n<\/p>\n<p>\nThe new discovery, detailed November 19 in <a href=\"http:\/\/stm.sciencemag.org\/content\/6\/263\/263ra161\" target=\"_blank\"><em>Science Translational Medicine<\/em><\/a>, shows how the two-pronged attack successfully hindered KRAS and other cellular processes to halt or shrink tumor growth.\n<\/p>\n<p>\nWhen activated, mutated KRAS clings to cell membranes and recruits proteins to ramp up cancer growth. Researchers have developed drugs to disable enzymes that tether KRAS to the cell membrane, but these drugs typically ended up being toxic because those enzymes are needed in the body for normal functions.\n<\/p>\n<p>\n\u201cThe Achilles\u2019 heel of KRAS is its movement to the membrane,\u201d says Verma, who is also holder of Salk\u2019s Irwin and Joan Jacobs Chair in Exemplary Life Science.\n<\/p>\n<div class=\"imageCaption530\"><img decoding=\"async\" alt=\"\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2014\/01\/2060-verma.jpg\"><\/p>\n<p>\nYifeng Xia and Inder Verma, professor of the Salk Laboratory of Genetics<\/p>\n<p><a target=\"_blank\" href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/02\/2060-verma.jpg\">Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.<\/p>\n<p>\nImagen: Cortes\u00eda del Instituto Salk de Estudios Biol\u00f3gicos\n<\/p>\n<\/div>\n<p>\nThe researchers took a new approach to targeting this membrane interaction when they noticed that a drug called Zometa, typically used to stop the breakdown and growth of cells in bone disease, also interfered with cell membrane interactions. In previous work, the team added carbon chains to a molecule similar to Zometa, to create a lipophilic bisphosphonate (BP) that blocked KRAS from attaching to the cell membrane.\n<\/p>\n<p>\n\u201cFor the first time, we had the ability to interfere with KRAS without being completely toxic,\u201d says Verma.\n<\/p>\n<p>\nThis, however, wasn\u2019t enough. Tumors were still proliferating, in part because the new BP led to failed attempts of a process called autophagy, where cells, under stress, self-destruct and break down into nutrients that can be used by other cells.\n<\/p>\n<p>\nAutophagy can be both good and bad in fighting cancer: in some cases, autophagy prompts cancer cells to die; in other settings, it creates a cellular environment that helps tumors thrive. With the BP treatment, cells began the process of autophagy but failed, leading to junk protein accumulation and an inflamed environment that helped the tumors to survive.\n<\/p>\n<p>\nBut, as demonstrated in the new work, when the researchers added a chemical called rapamycin, cells were able to carry out autophagy successfully and prevented tumor cells from proliferating. Rapamycin, discovered in the 1970s, is used in the clinic for preventing organ rejection and has also been linked to anti-cancer effects.\n<\/p>\n<div class=\"imageCaption\"><img decoding=\"async\" style=\"border-bottom: 1px #006699 solid;\" alt=\"\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2014\/01\/2060.jpg\"><\/p>\n<p>Mutation of the KRAS gene leads to a common and hard-to-treat lung cancer. A new combination therapy (lipophilic bisphosphonate and rapamycin) administered to mice for 40 days resulted in shrunken tumor size (right). <\/p>\n<p><a target=\"_blank\" href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/02\/2060.jpg\">Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.<\/p>\n<p>\nImagen: Cortes\u00eda del Instituto Salk de Estudios Biol\u00f3gicos\n<\/p>\n<\/div>\n<p>\n\u201cWe found if we also activated autophagy\u2013with the rapamycin\u2013and combine it with the inhibitor of the cell membrane\u2013the BP\u2013there were significant cell deaths in the tumors,\u201d says Yifeng Xia, Salk researcher and first author of the new work.\n<\/p>\n<p>\nWhen they injected the combination in mouse lung tumors, tumors shrunk or stopped growing. The study also found that a pancreatic cancer cell line responded to the dual treatment. Next, the team plans to test toxicity of the new BP. The group is also working with the <a href=\"http:\/\/cancer.ucsd.edu\/Pages\/default.aspx\" target=\"_blank\">University of California, San Diego, Moores Cancer Center<\/a> to design human clinical trials to test the dual therapy.\n<\/p>\n<p>\n\u201cThose two drugs have not been used together as far as we know for KRAS-related cancer treatment,\u201d adds Xia. \u201cWe are excited about the potential and that these molecules are already being used in clinical trials in some form.\u201d\n<\/p>\n<p>\nIn addition to Verma and Xia, authors on the paper included Shen Shen, Narayana Yeddula, Wolfgang Fischer and William Low of the Salk Institute; Yi-Liang Liu, Wei Zhu, Francisco Guerra and Eric Oldfield of the <a href=\"http:\/\/illinois.edu\/\" target=\"_blank\">University of Illinois at Urbana-Champaign<\/a>; and Yonghua Xie, Xiaoying Zhou and Yonghui Zhang of the <a href=\"http:\/\/www.tsinghua.edu.cn\/publish\/newthuen\/\" target=\"_blank\">Tsinghua University<\/a>.\n<\/p>\n<p>\nThe work was funded by the <a href=\"http:\/\/www.nih.gov\/\" target=\"_blank\">Institutos Nacionales de Salud<\/a>, Ipsen Biomeasure, the <a href=\"http:\/\/www.hnberger.org\/\" target=\"_blank\">H.N. and Frances C. Berger Foundation<\/a> and the <a href=\"http:\/\/helmsleytrust.org\/\" target=\"_blank\">Fundaci\u00f3n Ben\u00e9fica Leona M. y Harry B. Helmsley<\/a>.\n<\/p>\n<p>\n<strong>Acerca del Instituto Salk de Estudios Biol\u00f3gicos:<\/strong><br \/>\nThe Salk Institute for Biological Studies is one of the world&#8217;s preeminent basic research institutions, where internationally renowned faculty probes fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer&#8217;s, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.\n<\/p>\n<p>Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, MD, the Institute is an independent nonprofit organization and architectural landmark.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[115],"disease-research":[46,164,172],"class_list":["post-2514","disclosure","type-disclosure","status-publish","hentry","faculty-inder-verma","disease-research-cancer-biology","disease-research-lung-cancer","disease-research-pancreatic-cancer"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Salk scientists deliver a promising one-two punch for lung 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\/es\/news-release\/salk-scientists-deliver-a-promising-one-two-punch-for-lung-cancer\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Salk scientists deliver a promising one-two punch for lung cancer - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2013Scientists at the Salk Institute have discovered a powerful one-two punch for countering a common genetic mutation that often leads to drug-resistant cancers. 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