PMID- 21422725
OWN - NLM
STAT- MEDLINE
DCOM- 20110831
LR  - 20190911
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 115
IP  - 4
DP  - 2011
TI  - Pathophysiological response to hypoxia - from the molecular mechanisms of malady 
      to drug discovery: drug discovery for targeting the tumor microenvironment.
PG  - 446-52
AB  - The tumor microenvironment, characterized by regions of hypoxia, low nutrition, 
      and acidosis due to incomplete blood vessel networks, has been recognized as a 
      major factor that influences not only the response to conventional anti-cancer 
      therapies but also malignant progression and metastasis. However, exploiting such 
      a cumbersome tumor microenvironment for cancer treatment could provide 
      tumor-specific therapeutic approaches. In particular, hypoxia is now considered a 
      fundamentally important characteristic of the tumor microenvironment in which 
      hypoxia inducible factor (HIF)-1-mediated gene regulation is considered essential 
      for angiogenesis and tumor development. Additional oxygen sensitive signaling 
      pathways including mammalian target of rapamycin (mTOR) signaling and signaling 
      through activation of the unfolded protein response (UPR) also contribute to the 
      adaptation in the tumor microenvironment. This in turn has led to the current 
      extensive interest in the signal molecules related to adaptive responses in the 
      tumor microenvironment as potential molecular targets for cancer therapy against 
      refractory cancer and recurrence in preparation for the aging society. Therefore, 
      we should focus on the drug discovery for targeting the tumor microenvironment to 
      develop tumor-specific cytostatic agents including angiogenesis inhibitors. In 
      this paper, the development of hypoxia-selective prodrugs, HIF-1 inhibitors, and 
      modulators of the tumor microenvironment will be discussed.
FAU - Nagasawa, Hideko
AU  - Nagasawa H
AD  - Laboratory of Medicinal and Pharmaceutical Chemistry, Gifu Pharmaceutical 
      University, Japan. hnagasawa@gifu-pu.ac.jp
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20110316
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (Cytostatic Agents)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Prodrugs)
SB  - IM
MH  - Animals
MH  - Cytostatic Agents/pharmacology/therapeutic use
MH  - Drug Discovery/*methods
MH  - Humans
MH  - Hypoxia/*physiopathology
MH  - Hypoxia-Inducible Factor 1/*antagonists & inhibitors
MH  - Models, Biological
MH  - Molecular Targeted Therapy/*methods
MH  - Neoplasms/*drug therapy
MH  - Oxidation-Reduction
MH  - Prodrugs/pharmacology
MH  - Tumor Microenvironment/*drug effects
EDAT- 2011/03/23 06:00
MHDA- 2011/09/01 06:00
CRDT- 2011/03/23 06:00
PHST- 2011/03/23 06:00 [entrez]
PHST- 2011/03/23 06:00 [pubmed]
PHST- 2011/09/01 06:00 [medline]
AID - JST.JSTAGE/jphs/10R25FM [pii]
AID - 10.1254/jphs.10r25fm [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2011;115(4):446-52. doi: 10.1254/jphs.10r25fm. Epub 2011 Mar 16.