EPR: Evidence and fallacy
- PMID: 24794900
- DOI: 10.1016/j.jconrel.2014.03.057
EPR: Evidence and fallacy
Abstract
The enhanced permeability and retention (EPR) of nanoparticles in tumors has long stood as one of the fundamental principles of cancer drug delivery, holding the promise of safe, simple and effective therapy. By allowing particles preferential access to tumors by virtue of size and longevity in circulation, EPR provided a neat rationale for the trend toward nano-sized drug carriers. Following the discovery of the phenomenon by Maeda in the mid-1980s, this rationale appeared to be well justified by the flood of evidence from preclinical studies and by the clinical success of Doxil. Clinical outcomes from nano-sized drug delivery systems, however, have indicated that EPR is not as reliable as previously thought. Drug carriers generally fail to provide superior efficacy to free drug systems when tested in clinical trials. A closer look reveals that EPR-dependent drug delivery is complicated by high tumor interstitial fluid pressure (IFP), irregular vascular distribution, and poor blood flow inside tumors. Furthermore, the animal tumor models used to study EPR differ from clinical tumors in several key aspects that seem to make EPR more pronounced than in human patients. On the basis of this evidence, we believe that EPR should only be invoked on a case-by-case basis, when clinical evidence suggests the tumor type is susceptible.
Keywords: Clinical efficacy; Drug delivery; Enhanced permeability and retention; Intratumoral distribution; Tumor models.
Copyright © 2014 Elsevier B.V. All rights reserved.
Similar articles
-
Factors and mechanism of "EPR" effect and the enhanced antitumor effects of macromolecular drugs including SMANCS.Adv Exp Med Biol. 2003;519:29-49. doi: 10.1007/0-306-47932-X_2. Adv Exp Med Biol. 2003. PMID: 12675206 Review.
-
Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS.J Control Release. 2001 Jul 6;74(1-3):47-61. doi: 10.1016/s0168-3659(01)00309-1. J Control Release. 2001. PMID: 11489482 Review.
-
Elevating blood pressure as a strategy to increase tumor-targeted delivery of macromolecular drug SMANCS: cases of advanced solid tumors.Jpn J Clin Oncol. 2009 Nov;39(11):756-66. doi: 10.1093/jjco/hyp074. Epub 2009 Jul 11. Jpn J Clin Oncol. 2009. PMID: 19596662
-
[Arterial infusion chemotherapy with SMANCS].Nihon Rinsho. 2001 Oct;59 Suppl 6:629-33. Nihon Rinsho. 2001. PMID: 11762025 Review. Japanese. No abstract available.
-
Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect.Eur J Pharm Biopharm. 2009 Mar;71(3):409-19. doi: 10.1016/j.ejpb.2008.11.010. Epub 2008 Dec 3. Eur J Pharm Biopharm. 2009. PMID: 19070661 Review.
Cited by
-
Transvascular transport of nanocarriers for tumor delivery.Nat Commun. 2024 Sep 17;15(1):8172. doi: 10.1038/s41467-024-52416-0. Nat Commun. 2024. PMID: 39289401 Free PMC article. Review.
-
Advancing Ovarian Cancer Therapeutics: The Role of Targeted Drug Delivery Systems.Int J Nanomedicine. 2024 Sep 10;19:9351-9370. doi: 10.2147/IJN.S478313. eCollection 2024. Int J Nanomedicine. 2024. PMID: 39282574 Free PMC article. Review.
-
Defect-engineered chiral metal-organic frameworks.Mikrochim Acta. 2024 Jul 10;191(8):458. doi: 10.1007/s00604-024-06534-7. Mikrochim Acta. 2024. PMID: 38985164 Review.
-
Tumor versus Tumor Cell Targeting in Metal-Based Nanoparticles for Cancer Theranostics.Int J Mol Sci. 2024 May 10;25(10):5213. doi: 10.3390/ijms25105213. Int J Mol Sci. 2024. PMID: 38791253 Free PMC article. Review.
-
Enhancing glioma-specific drug delivery through self-assembly of macrophage membrane and targeted polymer assisted by low-frequency ultrasound irradiation.Mater Today Bio. 2024 Apr 25;26:101067. doi: 10.1016/j.mtbio.2024.101067. eCollection 2024 Jun. Mater Today Bio. 2024. PMID: 38706730 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources