{"id":10971,"date":"2024-05-30T09:29:41","date_gmt":"2024-05-30T14:29:41","guid":{"rendered":"https:\/\/www.wisconsin.edu\/all-in-wisconsin-new\/?post_type=campus_story&#038;p=10971"},"modified":"2024-05-30T09:29:41","modified_gmt":"2024-05-30T14:29:41","slug":"pancreatic-cancer-is-difficult-to-treat-nano-drugs-hitching-a-ride-on-bacteria-could-help","status":"publish","type":"campus_story","link":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/story\/pancreatic-cancer-is-difficult-to-treat-nano-drugs-hitching-a-ride-on-bacteria-could-help\/","title":{"rendered":"Pancreatic cancer is difficult to treat; nano-drugs hitching a ride on bacteria could help"},"content":{"rendered":"<figure id=\"attachment_10974\" aria-describedby=\"caption-attachment-10974\" style=\"width: 775px\" class=\"wp-caption aligncenter\"><a href=\"https:\/\/www.wisconsin.edu\/all-in-wisconsin-new\/wp-content\/uploads\/sites\/378\/2024\/05\/MAD_research_pancreas-cancer_QuanyinHu_phar062623_018-775x517-1.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-10974\" src=\"https:\/\/www.wisconsin.edu\/all-in-wisconsin-new\/wp-content\/uploads\/sites\/378\/2024\/05\/MAD_research_pancreas-cancer_QuanyinHu_phar062623_018-775x517-1.jpg\" alt=\"Photo of Quanyin Hu in his laboratory. Photo by Todd Brown\/UW\u2013Madison\" width=\"775\" height=\"517\" srcset=\"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-content\/uploads\/sites\/378\/2024\/05\/MAD_research_pancreas-cancer_QuanyinHu_phar062623_018-775x517-1.jpg 775w, https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-content\/uploads\/sites\/378\/2024\/05\/MAD_research_pancreas-cancer_QuanyinHu_phar062623_018-775x517-1-300x200.jpg 300w, https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-content\/uploads\/sites\/378\/2024\/05\/MAD_research_pancreas-cancer_QuanyinHu_phar062623_018-775x517-1-768x512.jpg 768w\" sizes=\"auto, (max-width: 775px) 100vw, 775px\" \/><\/a><figcaption id=\"caption-attachment-10974\" class=\"wp-caption-text\">Quanyin Hu in his laboratory. Photo by Todd Brown\/UW\u2013Madison<\/figcaption><\/figure>\n<p>Many pancreatic tumors are like malignant fortresses, surrounded by a dense matrix of collagen and other tissue that shields them from immune cells and immunotherapies that have been effective in treating other cancers. Employing bacteria to infiltrate that cancerous fortification and deliver these drugs could aid treatment for pancreatic cancer, according to newly published findings from a team of University of Wisconsin\u2013Madison researchers. Here\u2019s what to know:<\/p>\n<p><strong>Tumor collagen is a tough barrier:<\/strong>\u00a0Pancreatic cancer is well known for its deadliness and has among the lowest five-year survival rates among common cancers. While there are several drivers behind the disease\u2019s dismal prognosis, one that\u2019s the focus of this study is the matrix surrounding many pancreatic tumors, which acts as an effective barrier against treatment.<\/p>\n<ul>\n<li>The barrier is a collection of collagen, connective tissue, proteins that facilitate fibrosis and other cells. Recent studies have highlighted the role of this barrier in counteracting treatment attempts with immunotherapies \u2014 treatments that work by spurring on or tamping down the patient\u2019s immune system \u2014 such as immune checkpoint inhibitors.<\/li>\n<li>Analyzing patient tumor samples, the UW\u2013Madison team found genetic evidence that a specific type of collagen, called oncogenic collagen, is indeed a barrier to immunotherapy-based treatments.<\/li>\n<li>\u201cThat really dense extracellular matrix, made up of immunosuppressive cells, collagens and other cells, is a critical problem if we want to use immunotherapies against these pancreatic cancers,\u201d says\u00a0<a href=\"https:\/\/apps.pharmacy.wisc.edu\/sopdir\/quanyin_hu\/\">Quanyin Hu<\/a>, an assistant professor in the UW\u2013Madison School of Pharmacy. Hu led the study in collaboration with\u00a0<a href=\"https:\/\/www.surgery.wisc.edu\/staff\/sean-ronnekleiv-kelly\/\">Sean Ronnekleiv-Kelly<\/a>, a pancreatic surgeon and assistant professor in the UW\u2013Madison Department of Surgery.<\/li>\n<\/ul>\n<p><strong>A bacteria-based infiltration:<\/strong>\u00a0Hu is an expert in engineering cells for use as potential therapeutics or delivery vehicles for drugs. For this study,\u00a0<a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2666634024000837?via%3Dihub\">published in April in the journal Med<\/a>, Hu\u2019s lab applied a bacterium that could both penetrate through the tough collagen barrier and deliver immunotherapeutic \u201cnano-drugs.\u201d<\/p>\n<ul>\n<li>The team chose a strain of the bacterium\u00a0<em>Escherichia coli<\/em>\u00a0with a track record of safe use in humans and known affinity for low-oxygen environments such as tumors to serve as a drug delivery vehicle.<\/li>\n<li>Hu and his colleagues engineered \u201cprotein cages\u201d containing a pair of drugs \u2014 one breaks down collagen and the other is an anticancer immune checkpoint inhibitor \u2014 and attached them to the\u00a0<em>E. coli<\/em>.<\/li>\n<li>\u201c<em>E. coli<\/em>\u00a0has great motility, meaning it can move by itself, and it actively targets hypoxic environments like tumors,\u201d says Hu. \u201cAnd we found that it was able to penetrate deep into the tumor site to deliver drugs.\u201d<\/li>\n<\/ul>\n<p><strong>Approach shows promise in animal models:<\/strong>\u00a0The UW\u2013Madison team tested its\u00a0<em>E. coli<\/em>-based delivery system in mouse models of pancreatic ductal adenocarcinoma, or PDAC, the most common and lethal form of pancreatic cancer, which was the focus of the study.<\/p>\n<ul>\n<li>Mice treated with the therapeutic-laden bacteria experienced delayed tumor growth and significantly longer survival compared with mice that received other treatments.<\/li>\n<li>Postmortem analyses also showed that tumors treated with the nano-drug-carrying\u00a0<em>coli<\/em>\u00a0had the greatest infiltration of cancer-fighting immune cells among all treatments.<\/li>\n<li>\u201cRight now, treatment options are very limited for PDAC, and I hope this treatment approach can eventually lead to improvements in terms of survival and prognosis,\u201d says Hu.<\/li>\n<\/ul>\n<p>While this therapeutic approach shows promise for treating pancreatic cancer and other malignancies with tough collagen barriers, Hu\u2019s team is working on improving and simplifying it in animal models, with potential clinical trials still some time out.<\/p>\n<p><em>This research was supported by the University of Wisconsin Carbone Cancer Center Research Collaborative and Pancreas Cancer Research Task Force, UWCCC Transdisciplinary Cancer Immunology-Immunotherapy Pilot Project, and the start-up package from the University of Wisconsin\u2013Madison.<\/em><\/p>\n<hr \/>\n<p>Written by Will Cushman<\/p>\n<p>Link to original story: <a href=\"https:\/\/news.wisc.edu\/pancreatic-cancer-is-difficult-to-treat-nano-drugs-hitching-a-ride-on-bacteria-could-help\/\">https:\/\/news.wisc.edu\/pancreatic-cancer-is-difficult-to-treat-nano-drugs-hitching-a-ride-on-bacteria-could-help\/<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Many pancreatic tumors are like malignant fortresses, surrounded by a dense matrix of collagen and other tissue that shields them from immune cells and immunotherapies that have been effective in treating other cancers. Employing bacteria to infiltrate that cancerous fortification and deliver these drugs could aid treatment for pancreatic cancer, according to newly published findings [&hellip;]<\/p>\n","protected":false},"author":15,"featured_media":10974,"comment_status":"closed","ping_status":"closed","template":"","institution":[103],"story_category":[],"class_list":["post-10971","campus_story","type-campus_story","status-publish","has-post-thumbnail","hentry","institution-uw-madison"],"_links":{"self":[{"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/campus_story\/10971","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/campus_story"}],"about":[{"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/types\/campus_story"}],"author":[{"embeddable":true,"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/users\/15"}],"replies":[{"embeddable":true,"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/comments?post=10971"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/media\/10974"}],"wp:attachment":[{"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/media?parent=10971"}],"wp:term":[{"taxonomy":"institution","embeddable":true,"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/institution?post=10971"},{"taxonomy":"story_category","embeddable":true,"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/story_category?post=10971"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}