PMID- 11504502
OWN - NLM
STAT- Publisher
LR  - 20191120
IS  - 1532-2084 (Electronic)
IS  - 1368-7646 (Linking)
VI  - 2
IP  - 5
DP  - 1999 Oct
TI  - The tumor microenvironment as a determinant of drug response and resistance.
PG  - 285-288
AB  - Classically, studies of drug resistance in cancer have focused on the molecular 
      biology of single cancer cells. These types of studies have provided important 
      information regarding certain drug resistance mechanisms, including mechanisms 
      that reduce intracellular drug accumulation, alter or repair drug-induced damage, 
      and reduce drug-induced apoptosis. While these cellular mechanisms undoubtedly 
      contribute to the overall phenomenon of drug resistance, it is now evident that 
      the tumor cell microenvironment also influences how a tumor cell behaves and 
      responds to cytotoxic drugs or radiation. Two different forms of tumor 
      cell-environmental interaction may explain how some tumor cells survive initial 
      drug exposure and eventually express classical mechanisms of drug resistance. The 
      first form involves soluble mediators, such as interleukins, that are secreted by 
      non-tumor, stromal cells. Interleukin-6 (IL-6) is a classical example of how a 
      soluble mediator secreted by the tumor microenvironment is capable of enhancing 
      tumor cell survival and perhaps blocking apoptosis. The second form of tumor 
      cell-environment interaction requires direct cell contact and has been given the 
      term cell-adhesion-mediated drug resistance (CAM-DR). In this case, binding 
      extracellular matrix ligands in the tumor microenvironment may activate cell 
      adhesion molecules, such as the integrins, and these interactions result in the 
      activation of signal transduction pathways that block drug-induced apoptosis. 
      Interrupting the tumor cell-environment interactions or the associated signal 
      transduction pathways may represent a new approach for the treatment of cancer. 
      Copyright 1999 Harcourt Publishers Ltd.
FAU - Dalton, William S
AU  - Dalton WS
AD  - Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center, 
      University of South Florida, Tampa, Florida, USA
LA  - eng
PT  - Journal Article
PL  - Scotland
TA  - Drug Resist Updat
JT  - Drug resistance updates : reviews and commentaries in antimicrobial and 
      anticancer chemotherapy
JID - 9815369
EDAT- 2001/08/16 10:00
MHDA- 2001/08/16 10:00
CRDT- 2001/08/16 10:00
PHST- 2001/08/16 10:00 [pubmed]
PHST- 2001/08/16 10:00 [medline]
PHST- 2001/08/16 10:00 [entrez]
AID - S1368-7646(99)90097-3 [pii]
AID - 10.1054/drup.1999.0097 [doi]
PST - ppublish
SO  - Drug Resist Updat. 1999 Oct;2(5):285-288. doi: 10.1054/drup.1999.0097.