The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting

2001 ◽  
Vol 41 (1) ◽  
pp. 189-207 ◽  
Author(s):  
Hiroshi Maeda
Keyword(s):  
Drug Targeting ◽  
Tumor Vasculature ◽  
Epr Effect ◽  
Enhanced Permeability And Retention ◽  
Tumor Selective ◽  
Macromolecular Drug

scholarly journals EPR effect based nanocarriers targeting for treatment of cancer

2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Kavita Rai Gajbhiye ◽  
J M Gajbhiye
Keyword(s):  
Solid Tumors ◽  
Molecular Mechanisms ◽  
Drug Effects ◽  
Vascular Density ◽  
Epr Effect ◽  
Normal Tissues ◽  
Enhanced Permeability And Retention ◽  
Macromolecular Drugs ◽  
Intratumoral Delivery

<p>The enhanced permeability and retention (EPR) effect is a unique phenomenon of solid tumors related to their anatomical and pathophysiological differences from normal tissues. In solid tumors, angiogenesis leads to high vascular density. Large gaps exist between endothelial cells in tumor blood vessels, which lead to selective extravasations and retention of macromolecular drugs. This EPR effect served as a basis for development of macromolecular anticancer therapy. There are various factors, which lead to a significantly increased EPR effect and enhanced antitumor drug effects as well. This review discusses the unique anatomy of tumor vessels, molecular mechanisms of factors related to the EPR effect and the role of the EPR effect in the intratumoral delivery of protein and peptide drugs, macromolecular drugs and drug-loaded long-circulating nanocarriers.</p>

scholarly journals Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect

2021 ◽  
Vol 11 (2) ◽  
pp. 124
Author(s):  
Dong Huang ◽  
Lingna Sun ◽  
Leaf Huang ◽  
Yanzuo Chen
Keyword(s):  
Blood Vessels ◽  
Tumor Vessels ◽  
Epr Effect ◽  
Nanodrug Delivery ◽  
Enhanced Permeability And Retention ◽  
Macromolecular Drugs ◽  
Long Time ◽  
Vessel Network ◽  
Tumor Blood Vessels ◽  
The Relationship

The use of nanomedicine for antitumor therapy has been extensively investigated for a long time. Enhanced permeability and retention (EPR) effect-mediated drug delivery is currently regarded as an effective way to bring drugs to tumors, especially macromolecular drugs and drug-loaded pharmaceutical nanocarriers. However, a disordered vessel network, and occluded or embolized tumor blood vessels seriously limit the EPR effect. To augment the EPR effect and improve curative effects, in this review, we focused on the perspective of tumor blood vessels, and analyzed the relationship among abnormal angiogenesis, abnormal vascular structure, irregular blood flow, extensive permeability of tumor vessels, and the EPR effect. In this commentary, nanoparticles including liposomes, micelles, and polymers extravasate through the tumor vasculature, which are based on modulating tumor vessels, to increase the EPR effect, thereby increasing their therapeutic effect.

scholarly journals Secreted frizzled-related protein 2: a key player in noncanonical Wnt signaling and tumor angiogenesis

2020 ◽  
Author(s):  
Karlijn van Loon ◽  
Elisabeth J. M. Huijbers ◽  
Arjan W. Griffioen
Keyword(s):  
Wnt Signaling ◽  
Tumor Angiogenesis ◽  
Wnt Signaling Pathway ◽  
Tumor Vasculature ◽  
Great Promise ◽  
Cancer Therapies ◽  
Rich Domain ◽  
Metastatic Setting ◽  
Angiogenic Effect

Abstract Secreted frizzled-related proteins (SFRP) are glycoproteins containing a so-called frizzled-like cysteine-rich domain. This domain enables them to bind to Wnt ligands or frizzled (FzD) receptors, making potent regulators of Wnt signaling. As Wnt signaling is often altered in cancer, it is not surprising that Wnt regulators such as SFRP proteins are often differentially expressed in the tumor microenvironment, both in a metastatic and non-metastatic setting. Indeed, SFRP2 is shown to be specifically upregulated in the tumor vasculature of several types of cancer. Several studies investigated the functional role of SFRP2 in the tumor vasculature, showing that SFRP2 binds to FzD receptors on the surface of tumor endothelial cells. This activates downstream Wnt signaling and which is, thereby, stimulating angiogenesis. Interestingly, not the well-known canonical Wnt signaling pathway, but the noncanonical Wnt/Ca2+ pathway seems to be a key player in this event. In tumor models, the pro-angiogenic effect of SFRP2 could be counteracted by antibodies targeting SFRP2, without the occurrence of toxicity. Since tumor angiogenesis is an important process in tumorigenesis and metastasis formation, specific tumor endothelial markers such as SFRP2 show great promise as targets for anti-cancer therapies. This review discusses the role of SFRP2 in noncanonical Wnt signaling and tumor angiogenesis, and highlights its potential as anti-angiogenic therapeutic target in cancer.

scholarly journals Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1855 ◽  
Author(s):  
Lucia Salvioni ◽  
Maria Antonietta Rizzuto ◽  
Jessica Armida Bertolini ◽  
Laura Pandolfi ◽  
Miriam Colombo ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Safety Profile ◽  
Crucial Role ◽  
Clinical Relevance ◽  
Scientific Community ◽  
Design Development ◽  
Manufacturing Costs ◽  
Epr Effect ◽  
Enhanced Permeability And Retention ◽  
Cancer Nanomedicine

Starting with the enhanced permeability and retention (EPR) effect discovery, nanomedicine has gained a crucial role in cancer treatment. The advances in the field have led to the approval of nanodrugs with improved safety profile and still inspire the ongoing investigations. However, several restrictions, such as high manufacturing costs, technical challenges, and effectiveness below expectations, raised skeptical opinions within the scientific community about the clinical relevance of nanomedicine. In this review, we aim to give an overall vision of the current hurdles encountered by nanotherapeutics along with their design, development, and translation, and we offer a prospective view on possible strategies to overcome such limitations.

scholarly journals Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 761 ◽  
Author(s):  
Saori Yoshida ◽  
Hotaka Kawai ◽  
Takanori Eguchi ◽  
Shintaro Sukegawa ◽  
May Wathone Oo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Angiogenesis ◽  
Therapeutic Strategy ◽  
Hypoxia Inducible Factor ◽  
Tumor Vasculature ◽  
Clinical Specimens ◽  
Tumor Survival

CXCR4 is a chemokine receptor crucial in tumor progression, although the angiogenic role of CXCR4 in oral squamous cell carcinoma (OSCC) has not been investigated. Here we show that CXCR4 is crucial for tumor angiogenesis, thereby supporting tumor survival in OSCC. Immunohistochemistry on human clinical specimens revealed that CXCR4 and a tumor vasculature marker CD34 were co-distributed in tumor vessels in human OSCC specimens. To uncover the effects of CXCR4 inhibition, we treated the OSCC-xenografted mice with AMD3100, so-called plerixafor, an antagonist of CXCR4. Notably, we found a unique pathophysiological structure defined as tumor angiogenic inhibition triggered necrosis (TAITN), which was induced by the CXCR4 antagonism. Treatment with AMD3100 increased necrotic areas with the induction of hypoxia-inducible factor-1α in the xenografted tumors, suggesting that AMD3100-induced TAITN was involved in hypoxia and ischemia. Taken together, we demonstrated that CXCR4 plays a crucial role in tumor angiogenesis required for OSCC progression, whereas TAITN induced by CXCR4 antagonism could be an effective anti-angiogenic therapeutic strategy in OSCC treatment.

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