{"id":2511,"date":"2014-10-20T00:00:00","date_gmt":"2014-10-20T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/findings-point-to-an-off-switch-for-drug-resistance-in-cancer\/"},"modified":"2014-10-20T00:00:00","modified_gmt":"2014-10-20T07:00:00","slug":"findings-point-to-an-off-switch-for-drug-resistance-in-cancer","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/findings-point-to-an-off-switch-for-drug-resistance-in-cancer\/","title":{"rendered":"Findings point to an &#8220;off switch&#8221; for drug resistance in cancer"},"content":{"rendered":"<p>LA JOLLA\u2013Like a colony of bacteria or species of animals, <a href=\"https:\/\/www.salk.edu\/es\/ra\/cancer.html\/\">c\u00e1ncer<\/a> cells within a tumor must evolve to survive. A dose of chemotherapy may kill hundreds of thousands of cancer cells, for example, but a single cell with a unique mutation can survive and quickly generate a new batch of drug-resistant cells, making cancer hard to combat.\n<\/p>\n<p>\nNow, scientists at the Salk Institute have uncovered details about how cancer is able to become drug resistant over time, a phenomenon that occurs because cancer cells within the same tumor aren\u2019t identical\u2013the cells have slight genetic variation, or diversity. The new work, published October 20 in <a href=\"http:\/\/www.pnas.org\/content\/early\/2014\/10\/21\/1404656111\" target=\"_blank\"><em>PNAS<\/em><\/a>, shows how variations in breast cancer cells\u2019 RNA, the molecule that decodes genes and produces proteins, helps the cancer to evolve more quickly than previously thought. These new findings may potentially point to a \u201cswitch\u201d to turn off this diversity\u2013and thereby drug resistance\u2013in cancer cells.\n<\/p>\n<p><iframe src=\"\/\/www.youtube.com\/embed\/J6BJZvWUHI0\" frameborder=\"0\" allowfullscreen=\"\"><\/iframe><\/p>\n<p>\n\u201cIt\u2019s an inherent property of nature that in a community\u2013whether it is people, bacteria or cells\u2013a small number of members will likely survive different types of unanticipated environmental stress by maintaining diversity among its members,\u201d says the senior author of the new work, <a href=\"https:\/\/www.salk.edu\/es\/faculty\/emerson.html\/\">Beverly Emerson<\/a>, professor of Salk\u2019s <a href=\"https:\/\/www.salk.edu\/es\/faculty\/regulatory_biology_laboratory.html\/\">Laboratorio de Biolog\u00eda Reguladora<\/a> and holder of the Edwin K. Hunter Chair. \u201cCancer co-ops this diversification strategy to foster drug resistance.\u201d\n<\/p>\n<p>\nInstead of looking at a single gene or pathway to target with cancer therapies, lead author Fernando Lopez-Diaz, Salk staff scientist, and the team aim to uncover the diversification \u201cswitch\u201d by which cancer cells replicate but vary slightly from one another. Turning off this cellular process would strip cancer\u2019s ability to survive drug treatment.\n<\/p>\n<p>\n\u201cCancer isn\u2019t one cell but it\u2019s an ecosystem, a community of cells,\u201d says Emerson. \u201cThis study begins the groundwork for potentially finding a way to understand and dial back cell diversity and adaptability during chemotherapy to decrease drug resistance.\u201d\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\/2056.jpg\"><\/p>\n<p>Researchers use a small pipette (right) to extract and analyze the RNA of individual breast cancer cells to track a cancer cell line&#8217;s evolution.<\/p>\n<p><a target=\"_blank\" href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/02\/2056.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>\nTo uncover how groups of cancer cells achieve functional diversity (through RNA) to survive chemotherapy, Lopez-Diaz dosed dishes of human pre-cancer and metastatic breast cancer cells with the cancer drug paclitaxel for a week and then removed the drug for a few weeks, mimicking the treatment cycle for a cancer patient. Surviving cells\u2013usually one or two out of millions\u2013began to repopulate but with subtle changes in their RNA, presumably enabling them to survive future doses of the cancer drug.\n<\/p>\n<p>\nBy pushing the boundaries of bioinformatics, a collaboration led by Mei-Chong Wendy Lee and Nader Pourmand at the University of California, Santa Cruz charted more than 80,000 pieces of RNA per new cancer cell\u2013typically, single-cell studies by other approaches look at hundreds or so RNA pieces to distinguish fairly different cells from one another. This unusually thorough list helped the researchers tease out subtle differences between generations of same cancer cells treated with chemotherapy and chart how the cancer cell community increased diversity among its members through RNA.\n<\/p>\n<p>\n\u201cWe found an overwhelming return to diversity after chemotherapy treatment that couldn\u2019t be explained by expected mechanisms,\u201d says Lopez-Diaz. \u201cThere is something else going on here, a \u2018philosopher\u2019s stone\u2019 to cancer cell diversity that we now know to look for.\u201d\n<\/p>\n<p>\nAnd when the team analyzed the gene expression profiles of the surviving cancer cell line, they were again surprised. \u201cWe thought they\u2019d look like stressed cells with a few changes,\u201d says Emerson. \u201cInstead, after a few population doublings they go back to the normal gene expression pattern and rapidly reacquired drug sensitivity.\u201d This adaptive behavior, Emerson speculates, lets the group of cancer cells prepare for the next unanticipated threat.\n<\/p>\n<div class=\"imageCaption530\"><img decoding=\"async\" alt=\"\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2014\/01\/2056-Emerson-Lab.jpg\"><\/p>\n<p>\nFrom left: Yelena Dayn, Fernando J. Lopez Diaz and Beverly M. Emerson<\/p>\n<p><a target=\"_blank\" href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/02\/2056-Emerson-Lab.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>\nAnother intriguing finding of the paper was that a high percentage of precancerous cells that underwent chemotherapy survived and proliferated, more so than either normal or cancerous cells. This led the pre-cancer cells to become more drug tolerant once they became a tumor. \u201cThe pre-cancer cells, when exposed to chemotherapy, evolved much faster and create a more drug-resistant state,\u201d says Lopez-Diaz. \u201cThis and other findings can now be explored into greater detail using the knowledge and perspective we have gained here.\u201d\n<\/p>\n<p>\nAuthors of the work include Beverly M. Emerson, Fernando J. Lopez-Diaz and Yelena Dayn at the Salk Institute; Nader Pourmand, Mei-Chong Wendy Lee, Shahid Yar Khan, Muhammad Akram Tariq, Amie J. Radenbaugh, and Hyunsung John Kim of the <a href=\"http:\/\/www.ucsc.edu\/\" target=\"_blank\">University of California, Santa Cruz<\/a>; and Charles Joseph Vaske of <a href=\"http:\/\/five3genomics.com\/\" target=\"_blank\">Five3 Genomics<\/a>.\n<\/p>\n<p>\nFunding for the work includes support from the <a href=\"http:\/\/nih.gov\/\" target=\"_blank\">Institutos Nacionales de Salud<\/a>, the Chambers Medical Foundation, the GemCon Family Foundation and the <a href=\"http:\/\/www.tupperfoundation.org\/\" target=\"_blank\">Olive Tupper Foundation<\/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>\nFaculty 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":[82],"disease-research":[46],"class_list":["post-2511","disclosure","type-disclosure","status-publish","hentry","faculty-beverly-emerson","disease-research-cancer-biology"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Findings point to an &quot;off switch&quot; for drug resistance in 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\/findings-point-to-an-off-switch-for-drug-resistance-in-cancer\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Findings point to an &quot;off switch&quot; for drug resistance in cancer - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2013Like a colony of bacteria or species of animals, cancer cells within a tumor must evolve to survive. 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