{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:44:15Z","timestamp":1790347455472,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the US National Institutes of Health","award":["CA204345"],"award-info":[{"award-number":["CA204345"]}]},{"name":"the US National Institutes of Health","award":["CA235863"],"award-info":[{"award-number":["CA235863"]}]},{"name":"the US National Institutes of Health","award":["MDBR-20-135 SRS"],"award-info":[{"award-number":["MDBR-20-135 SRS"]}]},{"name":"the Samuel Waxman Cancer Research Foundation","award":["CA204345"],"award-info":[{"award-number":["CA204345"]}]},{"name":"the Samuel Waxman Cancer Research Foundation","award":["CA235863"],"award-info":[{"award-number":["CA235863"]}]},{"name":"the Samuel Waxman Cancer Research Foundation","award":["MDBR-20-135 SRS"],"award-info":[{"award-number":["MDBR-20-135 SRS"]}]},{"name":"the University of Pennsylvania Orphan Disease Center Million Dollar Bike Ride","award":["CA204345"],"award-info":[{"award-number":["CA204345"]}]},{"name":"the University of Pennsylvania Orphan Disease Center Million Dollar Bike Ride","award":["CA235863"],"award-info":[{"award-number":["CA235863"]}]},{"name":"the University of Pennsylvania Orphan Disease Center Million Dollar Bike Ride","award":["MDBR-20-135 SRS"],"award-info":[{"award-number":["MDBR-20-135 SRS"]}]},{"name":"he Chan Zuckerberg Initiative and a research contract with Panbela Therapeutics Inc.","award":["CA204345"],"award-info":[{"award-number":["CA204345"]}]},{"name":"he Chan Zuckerberg Initiative and a research contract with Panbela Therapeutics Inc.","award":["CA235863"],"award-info":[{"award-number":["CA235863"]}]},{"name":"he Chan Zuckerberg Initiative and a research contract with Panbela Therapeutics Inc.","award":["MDBR-20-135 SRS"],"award-info":[{"award-number":["MDBR-20-135 SRS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Polyamine biosynthesis is frequently dysregulated in cancers, and enhanced flux increases intracellular polyamines necessary for promoting cell growth, proliferation, and function. Polyamine depletion strategies demonstrate efficacy in reducing tumor growth and increasing survival in animal models of cancer; however, mechanistically, the cell-intrinsic and cell-extrinsic alterations within the tumor microenvironment underlying positive treatment outcomes are not well understood. Recently, investigators have demonstrated that co-targeting polyamine biosynthesis and transport alters the immune landscape. Although the polyamine synthesis-targeting drug 2-difluoromethylornithine (DFMO) is well tolerated in humans and is FDA-approved for African trypanosomiasis, its clinical benefit in treating established cancers has not yet been fully realized; however, combination therapies targeting compensatory mechanisms have shown tolerability and efficacy in animal models and are currently being tested in clinical trials. As demonstrated in pre-clinical models, polyamine blocking therapy (PBT) reduces immunosuppression in the tumor microenvironment and enhances the therapeutic efficacy of immune checkpoint blockade (ICB). Thus, DFMO may sensitize tumors to other therapeutics, including immunotherapies and chemotherapies.<\/jats:p>","DOI":"10.3390\/medsci10020031","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T22:37:20Z","timestamp":1655073440000},"page":"31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Polyamine Depletion Strategies in Cancer: Remodeling the Tumor Immune Microenvironment to Enhance Anti-Tumor Responses"],"prefix":"10.3390","volume":"10","author":[{"given":"Alexander","family":"Chin","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, MD 21250, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J.","family":"Bieberich","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, MD 21250, USA"},{"name":"University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8679-6414","authenticated-orcid":false,"given":"Tracy Murray","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Robert A.","family":"Casero","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nrd2243","article-title":"Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases","volume":"6","author":"Casero","year":"2007","journal-title":"Nat. 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