{"id":52474,"date":"2022-09-26T15:00:00","date_gmt":"2022-09-26T13:00:00","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=52474"},"modified":"2024-03-22T11:57:42","modified_gmt":"2024-03-22T10:57:42","slug":"combi-seq-a-leap-forward-for-personalised-cancer-therapy","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/combi-seq-a-leap-forward-for-personalised-cancer-therapy\/","title":{"rendered":"Combi-seq: a leap forward for personalised cancer therapy"},"content":{"rendered":"\n\n\n\n\n

Each year, around 10 million lives<\/a> around the world are cut short by cancer. While the last century of research has seen the number of approved anticancer drugs grow by leaps and bounds, the sheer diversity of disease forms and patient responses often defeats treatment strategies. The next revolution in anticancer therapeutics is likely to arrive in the form of drug combinations tailored specifically to a patient\u2019s own, unique tumour cells.<\/p>\n\n\n\n

A new study<\/a> from the group of Christoph Merten at the Swiss Federal Institute of Technology Lausanne (EPFL), started while he was a group leader at EMBL Heidelberg, proposes a new approach that will greatly increase the power of drug efficacy testing and pave the way for more personalised cancer therapy.<\/p>\n\n\n\n

The study was carried out in collaboration with the group of Julio Saez-Rodriguez, Professor at the Medical Faculty of Heidelberg University, a group leader at EMBL \u2013 University Hospital Heidelberg Molecular Medicine Partnership Unit (MMPU), and former group leader at EMBL-EBI, who supervised the computational analysis, led by Bence Szalai.<\/p>\n\n\n\n

Since every patient\u2019s tumour cells are different and continuously accumulate mutations, it is difficult to predict how they will react to a specific drug. The chance of tumour cells developing resistance to a particular drug is also high. For these reasons, combinations of two or more drugs are often considered more promising than single-drug chemotherapy. However, testing such combinations presents its own challenges.<\/p>\n\n\n\n

\u201cWhen testing the effects of drugs, we are limited by the amount of tissue we can obtain from patient biopsies, which is generally low. This means that with conventional technology, it’s impossible to screen hundreds of drug combinations for their effect on patient tumour cells,\u201d Merten said.<\/p>\n\n\n\n

Due to this reliance on large tissue volumes, present technologies can only test a handful of drug conditions at a time. They also usually provide purely yes-or-no answers, e.g. whether the cells live or die after treatment.<\/p>\n\n\n\n

However, Combi-seq \u2013 the new technique \u2013 overcomes this by cleverly using microfluidics \u2013 the precise control and manipulation of fluids with very miniaturised devices. Because of the low volume of liquids required, this allows researchers to carry out large-scale experiments with very small sample volumes. In 2018, Merten’s and Saez-Rodriguez\u2019s groups employed microfluidics to test<\/a> 56 anticancer drug combinations in cancer cells from patients.<\/p>\n\n\n\n

The present technique, established by former EMBL PhD student Lukas Mathur, takes this process even further, allowing researchers to test over 400 drug combinations with only a tiny amount of biological material.<\/p>\n\n\n\n

Combi-seq works by precise microfluidic manipulation of cells in solution. The researchers used this to isolate cells in droplets, each of which was only around a tenth of a millimetre in diameter. In addition to a cancer cell, each droplet contained a specific drug combination and a DNA sequence called a \u2018barcode\u2019, used as a label for the applied treatment condition. After 12 hours of treatment, the researchers could pool the cells, collect their genetic material for sequencing (identified by the \u2018barcodes\u2019), and analyse the results.<\/p>\n\n\n\n

\"\"
Testing anticancer drug combinations: the traditional approach. Credit: Aleksandra Krolik\/EMBL<\/figcaption><\/figure>\n\n\n\n
\"\"
Testing anticancer drug combinations: the Combi-seq approach. Credit: Aleksandra Krolik\/EMBL<\/figcaption><\/figure>\n\n\n\n

Not only does Combi-seq massively scale up how many treatment conditions can be tested simultaneously, it also allows scientists to gather accurate transcriptomics data from drug-exposed cells. It does so by incorporating next-generation sequencing into the workflow. Instead of just telling us whether a cell lives or dies after drug treatment, this method gives us a wealth of information about the cell\u2019s response that medical professionals might be able to draw upon while determining treatment strategies.<\/p>\n\n\n\n

\u201cUsing such transcriptomics data, we can make statements about how the signalling pathways in the cell react to the drug or about which genes are up- or downregulated in response. This is so much more powerful than anything we have had previously,\u201d Merten said.<\/p>\n\n\n\n

\u201cGenerating these datasets for different patients for a tumour type and applying advanced computational methods on them can improve our understanding of why drugs often do not work and ultimately improve patient care,\u201d said Julio Saez-Rodriguez.<\/p>\n\n\n\n

The method is both powerful and versatile. \u201cOur primary interest is in anticancer therapeutics,\u201d Merten said. \u201cHowever, this technique can potentially be extended to any conditions where one needs to analyse the response of primary human cells to drugs in detail.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"

Researchers have come up with a way to test the efficacy of hundreds of anticancer drug combinations \u2013 simultaneously, rapidly, and accurately.<\/p>\n","protected":false},"author":124,"featured_media":52554,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[38,981,43,353,654,195,247,653],"embl_taxonomy":[],"class_list":["post-52474","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-cancer","tag-drug","tag-heidelberg","tag-merten","tag-microfluidic-device","tag-microfluidics","tag-saez-rodriguez","tag-tumour"],"acf":{"featured":true,"show_featured_image":false,"field_target_display":"embl","field_article_language":{"value":"english","label":"English"},"article_intro":"

Researchers have come up with a way to test the efficacy of hundreds of anticancer drug combinations \u2013 simultaneously, rapidly, and accurately.<\/p>\n","related_links":[{"link_description":"Miniature testing of drug pairs on tumour biopsies","link_url":"https:\/\/www.embl.org\/news\/science\/miniature-testing-of-drug-pairs-on-tumour-biopsies\/"},{"link_description":"An ocean of droplets","link_url":"https:\/\/www.embl.org\/news\/picture-of-the-week\/potw2030\/"},{"link_description":"Sorting out HIV","link_url":"https:\/\/www.embl.org\/news\/science\/1705-sorting-out-hiv\/"},{"link_description":"Genome Biology Unit","link_url":"https:\/\/www.embl.org\/research\/units\/genome-biology\/"}],"source_article":[{"publication_title":"Combi-seq for multiplexed transcriptome-based profiling of drug combinations using deterministic barcoding in single-cell droplets","publication_link":{"title":"","url":"https:\/\/www.nature.com\/articles\/s41467-022-32197-0","target":""},"publication_authors":"Mathur L., Szalai B., et al","publication_source":"Nature Communications","publication_date":"1 Aug 2022","publication_doi":"10.1038\/s41467-022-32197-0"}],"in_this_article":false,"press_contact":"None","article_translations":false,"languages":""},"embl_taxonomy_terms":[],"yoast_head":"\nCombi-seq: a leap forward for personalised cancer therapy | EMBL<\/title>\n<meta name=\"description\" content=\"Researchers have come up with a way to test the efficacy of hundreds of anticancer drug combinations simultaneously.\" \/>\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\/combi-seq-a-leap-forward-for-personalised-cancer-therapy\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Combi-seq: a leap forward for personalised cancer therapy | EMBL\" \/>\n<meta property=\"og:description\" content=\"Researchers have come up with a way to test the efficacy of hundreds of anticancer drug combinations simultaneously.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science\/combi-seq-a-leap-forward-for-personalised-cancer-therapy\/\" \/>\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=\"2022-09-26T13:00:00+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-03-22T10:57:42+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/09\/Combiseq_Featured.png\" \/>\n\t<meta property=\"og:image:width\" content=\"1000\" \/>\n\t<meta property=\"og:image:height\" content=\"600\" 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