PMID- 21676290
OWN - NLM
STAT- MEDLINE
DCOM- 20111005
LR  - 20220317
IS  - 1462-3994 (Electronic)
IS  - 1462-3994 (Linking)
VI  - 13
DP  - 2011 May 13
TI  - Delivery of molecularly targeted therapy to malignant glioma, a disease of the 
      whole brain.
PG  - e17
LID - 10.1017/S1462399411001888 [doi]
AB  - Glioblastoma multiforme, because of its invasive nature, can be considered a 
      disease of the entire brain. Despite recent advances in surgery, radiotherapy and 
      chemotherapy, current treatment regimens have only a marginal impact on patient 
      survival. A crucial challenge is to deliver drugs effectively to invasive glioma 
      cells residing in a sanctuary within the central nervous system. The blood-brain 
      barrier (BBB) restricts the delivery of many small and large molecules into the 
      brain. Drug delivery to the brain is further restricted by active efflux 
      transporters present at the BBB. Current clinical assessment of drug delivery and 
      hence efficacy is based on the measured drug levels in the bulk tumour mass that 
      is usually removed by surgery. Mounting evidence suggests that the inevitable 
      relapse and lethality of glioblastoma multiforme is due to a failure to 
      effectively treat invasive glioma cells. These invasive cells hide in areas of 
      the brain that are shielded by an intact BBB, where they continue to grow and 
      give rise to the recurrent tumour. Effective delivery of chemotherapeutics to the 
      invasive glioma cells is therefore critical, and long-term efficacy will depend 
      on the ability of a molecularly targeted agent to penetrate an intact and 
      functional BBB throughout the entire brain. This review highlights the various 
      aspects of the BBB, and also the brain-tumour-cell barrier (a barrier due to 
      expression of efflux transporters in tumour cells), that together can 
      significantly influence drug response. It then discusses the challenge of glioma 
      as a disease of the whole brain, which lends emphasis to the need to deliver 
      drugs effectively across the BBB to reach both the central tumour and the 
      invasive glioma cells.
FAU - Agarwal, Sagar
AU  - Agarwal S
AD  - Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA.
FAU - Sane, Ramola
AU  - Sane R
FAU - Oberoi, Rajneet
AU  - Oberoi R
FAU - Ohlfest, John R
AU  - Ohlfest JR
FAU - Elmquist, William F
AU  - Elmquist WF
LA  - eng
GR  - R01 CA138437/CA/NCI NIH HHS/United States
GR  - CA138437/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20110513
PL  - England
TA  - Expert Rev Mol Med
JT  - Expert reviews in molecular medicine
JID - 100939725
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B/metabolism
MH  - Angiogenesis Inhibitors/administration & dosage/pharmacokinetics/*therapeutic use
MH  - Antibodies, Monoclonal/administration & dosage/pharmacokinetics/therapeutic use
MH  - Antineoplastic Agents/administration & dosage/pharmacokinetics/*therapeutic use
MH  - Biological Transport
MH  - *Blood-Brain Barrier
MH  - Brain/metabolism/pathology
MH  - Brain Neoplasms/*drug therapy/metabolism/pathology
MH  - Drug Delivery Systems
MH  - Drug Resistance, Neoplasm
MH  - Glioblastoma/*drug therapy/metabolism/pathology
MH  - Humans
MH  - *Molecular Targeted Therapy
PMC - PMC5048912
MID - NIHMS745695
EDAT- 2011/06/17 06:00
MHDA- 2011/10/06 06:00
PMCR- 2016/10/04
CRDT- 2011/06/17 06:00
PHST- 2011/06/17 06:00 [entrez]
PHST- 2011/06/17 06:00 [pubmed]
PHST- 2011/10/06 06:00 [medline]
PHST- 2016/10/04 00:00 [pmc-release]
AID - S1462399411001888 [pii]
AID - 10.1017/S1462399411001888 [doi]
PST - epublish
SO  - Expert Rev Mol Med. 2011 May 13;13:e17. doi: 10.1017/S1462399411001888.