{"id":130,"date":"2020-05-13T13:58:53","date_gmt":"2020-05-13T10:58:53","guid":{"rendered":"https:\/\/sites.uef.fi\/drug-targeting\/?page_id=130"},"modified":"2026-07-03T09:10:45","modified_gmt":"2026-07-03T06:10:45","slug":"cancer-cell-targeting","status":"publish","type":"page","link":"https:\/\/sites.uef.fi\/drug-targeting\/projects\/cancer-cell-targeting\/","title":{"rendered":"Cancer Cell Targeting"},"content":{"rendered":"\n<p>Cancer cells often exhibit altered expression of membrane transporters to support their increased demand for nutrients and rapid proliferation. Many members of the Solute Carrier (SLC) family are overexpressed in tumors and can be exploited for selective drug delivery. ATP-binding cassette (ABC) transporters also play important roles in cancer biology and drug resistance by regulating the efflux of therapeutic agents. Together, these transport systems offer unique opportunities for developing more effective and selective cancer therapies.<\/p>\n\n\n\n<p>Our research focuses on two complementary approaches:<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">1. SLC-mediated delivery of chemotherapeutics<\/h5>\n\n\n\n<p>Developing drugs, prodrugs, and drug analogues that utilize transporters, such as L-type Amino Acid Transporter 1 (LAT1), and organic cation transporter 1 and 3 (OCT1\/OCT3) to achieve selective accumulation in cancer cells and tumors.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">2. Targeting the tumor microenvironment and angiogenesis<\/h5>\n\n\n\n<p>Beyond transporter-mediated drug delivery, we are interested in understanding how the tumor microenvironment and hypoxia regulate transporter expression and function in cancer cells. These mechanisms influence nutrient uptake, drug distribution, and tumor progression, and may reveal new opportunities for transporter-based therapeutic interventions.<\/p>\n\n\n\n<p><strong>Through these approaches, we aim to develop novel transporter-based strategies that improve the selectivity and effectiveness of cancer therapies.<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-image size-full is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"719\" height=\"436\" src=\"https:\/\/sites.uef.fi\/drug-targeting\/wp-content\/uploads\/sites\/59\/2022\/12\/Hypoxia.png\" alt=\"\" class=\"wp-image-1467\" style=\"width:584px;height:auto\" srcset=\"https:\/\/sites.uef.fi\/drug-targeting\/wp-content\/uploads\/sites\/59\/2022\/12\/Hypoxia.png 719w, https:\/\/sites.uef.fi\/drug-targeting\/wp-content\/uploads\/sites\/59\/2022\/12\/Hypoxia-300x182.png 300w\" sizes=\"auto, (max-width: 719px) 100vw, 719px\" \/><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\">Selected Publications<\/h2>\n\n\n\n<p><b><u>1. LAT1-Utilizing Prodrugs of Chemotherapeutics or Efflux Transporter Inhibitors<\/u><\/b><\/p>\n\n\n\n<p>Bahrami, K.; K\u00e4rkk\u00e4inen, J.; Bibi, S.; Huttunen, J.; Tampio, J.; Montaser, A. B.; Moody, C. L.; Lehtonen, M.; Rautio, J.; Wheelhouse, R.T.; <strong>Huttunen, K. M.<\/strong> Selective Transport of Temozolomide Does Not Override DNA Repair-mediated Chemoresistance. <strong><em>European Journal of Pharmaceutical Sciences<\/em>, 2024<\/strong>, <em>195<\/em>:106661. <a href=\"https:\/\/doi.org\/10.1016\/j.ejps.2023.106661\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/doi.org\/0.1016\/j.ejps.2023.106661<\/a><\/p>\n\n\n\n<p>Huttunen, J.; Tampio, J.; J\u00e4rvinen, J.; Montaser, A.B.; Markowicz-Piasecka, M.; <strong>Huttunen, K. M.<\/strong> Amino Acid Derivative of Probenecid Potentiates Apoptosis-Inducing Effects of Vinblastine by Increasing Oxidative Stress in a Cancer Cell-Specific Manner. <strong><em>Chemico-Biological Interactions<\/em><\/strong>, <strong>2024<\/strong>, <em>388<\/em>: 110833. <a href=\"https:\/\/doi.org\/10.1016\/j.cbi.2023.110833\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/doi.org\/10.1016\/j.cbi.2023.110833<\/a><\/p>\n\n\n\n<p>Markowicz-Piasecka, M.; Huttunen, J.; Montaser, A.; Adla. S. K.; Auriola, S.; Lehtonen, M.;&nbsp;Huttunen K M. Ganciclovir and Its Hemocompatible More Lipophilic Derivative Can Enhance the Apoptotic Effects of Methotrexate by Inhibiting Breast Cancer Resistance Protein (BCRP).<strong><em> International Journal of Molecular Sciences<\/em><\/strong>, <strong>2021<\/strong>, <em>22<\/em>(14): 7727. <a href=\"https:\/\/doi.org\/10.3390\/ijms22147727\" target=\"_blank\" rel=\"noopener\">https:\/\/doi.org\/<span class=\"citation-doi\">10.3390\/ijms22147727<\/span><\/a><\/p>\n\n\n\n<p>Montaser, A.; Markowicz-Piasecka, M.; Sikora, J.; Jalkanen, J.; Huttunen, K. M. L-Type Amino acid Transporter 1 (LAT1)-Utilizing Efflux Transporter Inhibitors Can Improve the Brain Uptake and Apoptosis-Inducing Effects of Vinblastine in Cancer Cells. <strong><em>International Journal of Pharmaceutics<\/em><\/strong>, <strong>2020<\/strong>, <em>586<\/em>, 119585<em>. <\/em><a href=\"https:\/\/doi.org\/10.1016\/j.ijpharm.2020.119585\" target=\"_blank\" rel=\"noopener noreferrer\">https:\/\/doi.org\/10.1016\/j.ijpharm.2020.119585<\/a><\/p>\n\n\n\n<p>Huttunen J.; Gynther, M.; Huttunen, K. M. Targeted Efflux Transporter Inhibitors \u2013 A Solution to Improve Poor Cellular Accumulation of Anti-cancer Agents. <b><i>International Journal of Pharmaceutics<\/i><\/b>, <b>2018<\/b>, <i>550<\/i>, 278-289. <a href=\"https:\/\/doi.org\/10.1016\/j.ijpharm.2018.08.047\" target=\"_blank\" rel=\"noopener noreferrer\">https:\/\/doi.org\/10.1016\/j.ijpharm.2018.08.047<\/a><\/p>\n\n\n\n<p><b><u>2. OCTs as Novel Anti-Cancer Carriers&nbsp;<\/u><\/b><\/p>\n\n\n\n<p>Kuorikoski, V.; Tampio, J.; Kerachni, S.; Timonen, D.; Tonduru, A. K.; Markowicz-Piasecka, M.; Terasaki, T.; Poso, A.; Huttunen, K. M. Enhanced Polarity of Sulfonamide Metformin Derivatives Increases Cellular Uptake and Apoptosis-Inducing Effects in Human Breast Cancer Cells. <strong><em>Molecular Pharmaceutics<\/em><\/strong><em>, <strong>2026<\/strong><\/em>, <em>23<\/em>(2):680-693. <a href=\"http:\/\/doi.org\/10.1021\/acs.molpharmaceut.5c00432\" target=\"_blank\" rel=\"noreferrer noopener\">http:\/\/doi.org\/10.1021\/acs.molpharmaceut.5c00432<\/a><\/p>\n\n\n\n<p>Markowicz-Piasecka, M.; Huttunen, J.; Zajda, A.; Sikora, J.; Huttunen, K. M. Sulfonamide Metformin Derivatives Induce Mitochondrial-Associated Apoptosis and Cell Cycle Arrest in Breast Cancer Cells. <strong><em>Chemico-Biological Interactions<\/em><\/strong>, <strong>2022<\/strong>, <em>352<\/em>, 109795<em>. <\/em><a href=\"https:\/\/doi.org\/10.1016\/j.cbi.2021.109795\" target=\"_blank\" rel=\"noopener\">https:\/\/doi.org\/<span class=\"citation-doi\">10.1016\/j.cbi.2021.109795<\/span><\/a><\/p>\n\n\n\n<p>Markowicz-Piasecka, M.; Sadowski, K.; Huttunen, J.; Sikora, J.; Huttunen, K.M. Incorporation of Sulfonamide Moiety into Biguanide Scaffold Results in Apoptosis Induction and Cell Cycle Arrest in MCF-7 Breast Cancer Cells. <strong><em>International Journal of Molecular Sciences<\/em><\/strong>,<strong> 2021<\/strong>, <em>22<\/em>(11): 5642. <a href=\"https:\/\/doi.org\/10.3390\/ijms22115642\" target=\"_blank\" rel=\"noopener\">https:\/\/doi.org\/10.3390\/ijms22115642<\/a><\/p>\n\n\n\n<p>Markowicz-Piasecka, M.; Komeil, I.; Huttunen, J.; Sikora, J.; Huttunen, K. M. Effective cellular transport of ortho-halogenated sulfonamide derivatives of metformin is related with improved antiproliferative activity and apoptosis induction in MCF-7 cells. <b><i>International Journal of Molecular Sciences<\/i><\/b>, <b>2020<\/b>, <i>21<\/i>, 2389-2417. <a href=\"https:\/\/doi.org\/10.1016\/j.bioorg.2019.03.036\" target=\"_blank\" rel=\"noopener noreferrer\">https:\/\/doi.org\/10.1016\/j.bioorg.2019.03.036<\/a><\/p>\n\n\n\n<p>Markowicz-Piasecka M, Huttunen J, Sikora J, Huttunen KM. Sulfenamide derivatives can improve transporter-mediated cellular uptake of metformin and induce cytotoxicity in human breast adenocarcinoma cell lines. <b><i>Bioorganic Chemistry<\/i><\/b>, <b>2019<\/b>, <i>87<\/i>, 321-334. <a href=\"http:\/\/doi.org\/10.1016\/j.bioorg.2019.03.036\" target=\"_blank\" rel=\"noopener noreferrer\">http:\/\/doi.org\/10.1016\/j.bioorg.2019.03.036<\/a><\/p>\n\n\n\n<p><b><u>3. Inhibitors of LAT1 as a Novel Anti-Cancer Agents <\/u><\/b><\/p>\n\n\n\n<p>Huttunen, K. M.; Gynther, M.; Huttunen, J.; Puris, E.; Spicer, J. A.; Denny, W. A. A Selective and Slowly Reversible Inhibitor of L-Type Amino Acid Transporter 1 (LAT1) Potentiates Antiproliferative Drug Efficacy in Cancer Cells. <b><i>Journal of Medicinal Chemistry<\/i><\/b>, <b>2016<\/b>, <i>59<\/i> (12), 5740-5751. <a href=\"http:\/\/doi.org\/10.1021\/acs.jmedchem.6b00190\" target=\"_blank\" rel=\"noopener noreferrer\">http:\/\/doi.org\/10.1021\/acs.jmedchem.6b00190<\/a><\/p>\n\n\n\n<p>Markowicz-Piasecka, M.; Huttunen, J.; Montaser, A.; Huttunen, K. M.&nbsp; Hemocompatible LAT1-inhibitor Can Induce Apoptosis in Cancer Cells Without Affecting Brain Amino Acid Homeostasis. <strong><em>Apoptosis<\/em><\/strong>, <strong>2020<\/strong>, <em>25<\/em>(5), 426-440. <a href=\"http:\/\/doi.org\/10.1007\/s10495-020-01603-7\" target=\"_blank\" rel=\"noopener noreferrer\">http:\/\/doi.org\/10.1007\/s10495-020-01603-7<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Cancer cells often exhibit altered expression of membrane transporters to support their increased demand for nutrients and rapid proliferation. Many members of the Solute Carrier (SLC) family are overexpressed in tumors and can be exploited for selective drug delivery. ATP-binding cassette (ABC) transporters also play important roles in cancer biology and drug resistance by regulating [&hellip;]<\/p>\n","protected":false},"author":140,"featured_media":0,"parent":43,"menu_order":2,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"class_list":["post-130","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.7 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Cancer Cell Targeting - Transporter Targeted Drug Delivery<\/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:\/\/sites.uef.fi\/drug-targeting\/projects\/cancer-cell-targeting\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Cancer Cell Targeting - Transporter Targeted Drug Delivery\" \/>\n<meta property=\"og:description\" content=\"Cancer cells often exhibit altered expression of membrane transporters to support their increased demand for nutrients and rapid proliferation. 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