{"id":8051,"date":"2016-09-26T17:00:21","date_gmt":"2016-09-26T15:00:21","guid":{"rendered":"https:\/\/news.embl.de\/?p=8051"},"modified":"2024-03-25T10:16:20","modified_gmt":"2024-03-25T09:16:20","slug":"1609-turning-up-heat-drug-side-effects","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/1609-turning-up-heat-drug-side-effects\/","title":{"rendered":"Turning up the heat on drug side effects"},"content":{"rendered":"\n

By tracking the impact of a widely used leukaemia drug on proteins inside living cells, research led by EMBL and Cellzome has shed light on the molecular causes of the drug\u2019s side effects. Published in Nature Chemical Biology<\/em>, the study also indicates that the drug has potential to be repurposed to treat tyrosinemia, a rare genetic disorder that can lead to liver, kidney and neurological problems.<\/p>\n\n\n\n

Many drugs used in the treatment of cancer have severe side effects. These occur when the drugs affect not only the target proteins in tumour cells, but also proteins in healthy cells. By identifying proteins that are inadvertently targeted by anti-cancer drugs, scientists aim to learn more about who might be affected, how and why, in order to better inform treatment.<\/p>\n\n\n\n

Warming up<\/h2>\n\n\n\n

Two years ago, at drug discovery company Cellzome, an international team led by Mikhail Savitski developed an elegant method known as thermal proteome profiling, which they believe can provide answers to such puzzles. By heating up cancer cells, the technique enables researchers to compare the \u2018melting\u2019 behaviours of individual proteins before and after the administration of a cancer drug, ultimately revealing which proteins the drug is targeting.<\/p>\n\n\n\n

\u201cAfter we developed this technology I could not stop thinking about ways to develop it and apply it in different settings \u2013 it opens up some very exciting research paths,\u201d explains Savitski, who joined EMBL as a group leader <\/a>this year.<\/p>\n\n\n\n

Sidetracked<\/h2>\n\n\n\n

One of these paths emerged out of the blue. The team were developing a refined version of the technology using a drug for multiple myeloma \u2013 a type of leukaemia that affects plasma cells. In some patients, the drug, panobinostat, causes a variety of serious side effects, including hyperthyroidism.<\/p>\n\n\n\n

In the study, Savitski and colleagues identified an unexpected target of the drug: a protein called phenylalanine hydroxylase (PAH). As its name implies, PAH acts on phenylalanine. Phenylalanine is an amino acid, one of the building blocks proteins are made of, so it is essential for life. But too much phenylalanine can lead to problems including neurological damage and hyperthyroidism. Since PAH\u2019s job in the cell is to convert phenylalanine into another amino acid \u2013 tyrosine \u2013 this explained how panobinostat can cause hyperthyroidism. The leukaemia drug inadvertently targets PAH, phenylalanine is not converted to tyrosine as it should be, so it accumulates in a patient\u2019s cells. \u201cOur study underscores the importance of monitoring amino acid levels in patients and the need to take caution when applying the drug,\u201d says Marcus Bantscheff, head of technology at Cellzome, who co-led the study.<\/p>\n\n\n\n

The research, which was supported by colleagues from Utrecht University<\/a> and the University of Texas Health Science Center<\/a>, also identifies panobinostat as the first drug capable of inhibiting PAH, opening up potential avenues for repurposing it to tackle other illnesses. \u201cIt could provide an opportunity to develop treatments for diseases where PAH plays a big role, such as tyrosinemia,\u201d adds Isabelle Becher, the first author of the study. \u201cThe study provides an ideal starting point from which one can look to develop a drug that is really specific.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"

Side-effects of leukaemia drug explained, reveal possibility of repurposing to treat other diseases<\/p>\n","protected":false},"author":10,"featured_media":8054,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[32,43,71,45,434],"embl_taxonomy":[],"class_list":["post-8051","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-health","tag-heidelberg","tag-industry","tag-proteomics","tag-savitski"],"acf":{"article_intro":"

Side-effects of leukaemia drug explained, reveal possibility of repurposing to treat other diseases<\/p>\n","related_links":[{"link_description":"Cellzome","link_url":"http:\/\/www.gsk.com\/en-gb\/research\/randd-locations\/europe\/cellzome\/"},{"link_description":"Savitski team","link_url":"http:\/\/www.embl.de\/research\/units\/genome_biology\/savitski\/index.html"},{"link_description":"Welcome to EMBL: Mikhail Savitski","link_url":"https:\/\/news.embl.de\/science\/1609-welcome-mikhail-savitski\/"}],"article_sources":[{"source_description":"

Becher I et al.<\/em> Nature Chemical Biology<\/em>, published online 26 September 2016. DOI: 10.1038\/nchembio.2185<\/p>\n","source_link_url":"http:\/\/dx.doi.org\/10.1038\/nchembio.2185"}],"vf_locked":false,"featured":false,"color":"#007B53"},"embl_taxonomy_terms":[],"yoast_head":"\nTurning up the heat on drug side effects<\/title>\n<meta name=\"description\" content=\"Side-effects of leukaemia drug explained, reveal possibility of repurposing to treat other diseases\" \/>\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.embl.org\/news\/science\/1609-turning-up-heat-drug-side-effects\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Turning up the heat on drug side effects\" \/>\n<meta property=\"og:description\" content=\"Side-effects of leukaemia drug explained, reveal possibility of repurposing to treat other diseases\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science\/1609-turning-up-heat-drug-side-effects\/\" \/>\n<meta property=\"og:site_name\" content=\"EMBL\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/embl.org\/\" \/>\n<meta property=\"article:published_time\" content=\"2016-09-26T15:00:21+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-03-25T09:16:20+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/09\/1609-turning-up-the-heat-1.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"620\" \/>\n\t<meta property=\"og:image:height\" content=\"425\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Adam Gristwood\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@embl\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Adam Gristwood\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"NewsArticle\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1609-turning-up-heat-drug-side-effects\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1609-turning-up-heat-drug-side-effects\/\"},\"author\":{\"name\":\"Adam Gristwood\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/f7c8259826dbd1b46613f2b3c6d88953\"},\"headline\":\"Turning up the heat on drug side effects\",\"datePublished\":\"2016-09-26T15:00:21+00:00\",\"dateModified\":\"2024-03-25T09:16:20+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1609-turning-up-heat-drug-side-effects\/\"},\"wordCount\":524,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1609-turning-up-heat-drug-side-effects\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/09\/1609-turning-up-the-heat-1.jpg\",\"keywords\":[\"health\",\"heidelberg\",\"industry\",\"proteomics\",\"savitski\"],\"articleSection\":[\"Science\",\"Science & Technology\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1609-turning-up-heat-drug-side-effects\/\",\"url\":\"https:\/\/www.embl.org\/news\/science\/1609-turning-up-heat-drug-side-effects\/\",\"name\":\"Turning up the heat on drug side effects\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1609-turning-up-heat-drug-side-effects\/#primaryimage\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1609-turning-up-heat-drug-side-effects\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/09\/1609-turning-up-the-heat-1.jpg\",\"datePublished\":\"2016-09-26T15:00:21+00:00\",\"dateModified\":\"2024-03-25T09:16:20+00:00\",\"description\":\"Side-effects of leukaemia drug explained, reveal possibility of repurposing to treat other diseases\",\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/www.embl.org\/news\/science\/1609-turning-up-heat-drug-side-effects\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1609-turning-up-heat-drug-side-effects\/#primaryimage\",\"url\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/09\/1609-turning-up-the-heat-1.jpg\",\"contentUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/09\/1609-turning-up-the-heat-1.jpg\",\"width\":620,\"height\":425,\"caption\":\"Histopathological image of multiple myeloma. 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