PMID- 25526702
OWN - NLM
STAT- MEDLINE
DCOM- 20151123
LR  - 20220317
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 201
DP  - 2015 Mar 10
TI  - Improving drug delivery to solid tumors: priming the tumor microenvironment.
PG  - 78-89
LID - S0168-3659(14)00815-3 [pii]
LID - 10.1016/j.jconrel.2014.12.018 [doi]
AB  - Malignant transformation and growth of the tumor mass tend to induce changes in 
      the surrounding microenvironment. Abnormality of the tumor microenvironment 
      provides a driving force leading not only to tumor progression, including 
      invasion and metastasis, but also to acquisition of drug resistance, including 
      pharmacokinetic (drug delivery-related) and pharmacodynamic (sensitivity-related) 
      resistance. Drug delivery systems exploiting the enhanced permeability and 
      retention (EPR) effect and active targeting moieties were expected to be able to 
      cope with delivery-related drug resistance. However, recent evidence supports a 
      considerable barrier role of tumors via various mechanisms, which results in 
      imperfect or inefficient EPR and/or targeting effect. The components of the tumor 
      microenvironment such as abnormal tumor vascular system, deregulated composition 
      of the extracellular matrix, and interstitial hypertension (elevated interstitial 
      fluid pressure) collectively or cooperatively hinder the drug distribution, which 
      is prerequisite to the efficacy of nanoparticles and small-molecule drugs used in 
      cancer medicine. Hence, the abnormal tumor microenvironment has recently been 
      suggested to be a promising target for the improvement of drug delivery to 
      improve therapeutic efficacy. Strategies to modulate the abnormal tumor 
      microenvironment, referred to here as "solid tumor priming" (vascular 
      normalization and/or solid stress alleviation leading to improvement in blood 
      perfusion and convective molecular movement), have shown promising results in the 
      enhancement of drug delivery and anticancer efficacy. These strategies may 
      provide a novel avenue for the development of new chemotherapeutics and 
      combination chemotherapeutic regimens as well as reassessment of previously 
      ineffective agents.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Khawar, Iftikhar Ali
AU  - Khawar IA
AD  - Department of Biomedicine & Health Sciences, Graduate School, The Catholic 
      University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 137-701, Republic of 
      Korea.
FAU - Kim, Jung Ho
AU  - Kim JH
AD  - Department of Biomedicine & Health Sciences, Graduate School, The Catholic 
      University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 137-701, Republic of 
      Korea.
FAU - Kuh, Hyo-Jeong
AU  - Kuh HJ
AD  - Department of Biomedicine & Health Sciences, Graduate School, The Catholic 
      University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 137-701, Republic of 
      Korea; Department of Medical LifeScience, School of Medicine, The Catholic 
      University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 137-701, Republic of 
      Korea. Electronic address: hkuh@catholic.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20141217
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage
MH  - *Drug Delivery Systems
MH  - Humans
MH  - Neoplasms/*drug therapy/metabolism
MH  - *Tumor Microenvironment
OTO - NOTNLM
OT  - Drug efficacy
OT  - Solid stress
OT  - Tumor microenvironment
OT  - Tumor priming
OT  - Tumor stroma
OT  - Vascular normalization
EDAT- 2014/12/21 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/12/21 06:00
PHST- 2014/07/25 00:00 [received]
PHST- 2014/12/15 00:00 [revised]
PHST- 2014/12/16 00:00 [accepted]
PHST- 2014/12/21 06:00 [entrez]
PHST- 2014/12/21 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S0168-3659(14)00815-3 [pii]
AID - 10.1016/j.jconrel.2014.12.018 [doi]
PST - ppublish
SO  - J Control Release. 2015 Mar 10;201:78-89. doi: 10.1016/j.jconrel.2014.12.018. 
      Epub 2014 Dec 17.