PMID- 15989502
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20050712
LR  - 20050701
IS  - 1744-7623 (Electronic)
IS  - 1472-8214 (Linking)
VI  - 6
IP  - 1
DP  - 2001 Apr
TI  - Tumour angiogenesis: a novel therapeutic target in patients with malignant 
      disease.
PG  - 155-74
AB  - Angiogenesis refers to the formation of new blood vessels from an existing 
      vasculature and is recognised as a necessary requirement for most tumours to grow 
      beyond 1-2 mm in diameter. Factors established as playing a role in angiogenesis 
      may be divided into two principal groups: (a) those that stimulate endothelial 
      cell proliferation and/or elongation, migration and vascular morphogenesis 
      including vascular endothelial growth factor (VEGF), basic fibroblast growth 
      factor (bFGF), platelet derived endothelial cell growth factor (PD-ECGF) and the 
      tie and tek receptors, and (b) proteases and their receptors involved in the 
      breakdown of basement membranes and the extracellular matrix (ECM) including the 
      matrix metalloproteinases (MMPs), cathepsins and those involved in the plasmin 
      cascade. Angiogenesis has been identified as a potential target for development 
      of anticancer agents. The discovery of a range of naturally-occurring factors 
      which negatively regulate angiogenesis, including the thrombospondins, 
      angiostatin and endostatin, and the tissue inhibitors of MMPs (TIMPs), has given 
      added impetus to this approach. Synthetic anti-angiogenic compounds have been 
      developed, including TNP-470, carboxyamidotriazole, VEGF-tyrosine kinase 
      inhibitors and MMP inhibitors (MMPI) which, like the naturally-occurring 
      anti-angiogenic factors, inhibit angiogenesis in vitro and in vivo, and tumour 
      development, growth and metastasis in vivo. Anti-angiogenic agents also enhance 
      the antitumour activity of many conventional cytotoxic chemotherapeutic agents. 
      Such combinations may have a particular role as adjuvant therapies following 
      surgical resection of primary tumours. Unlike tumour cells, tumour associated 
      endothelial cells do not develop resistance to anti-angiogenic agents. 
      Furthermore, anti-angiogenic agents are generally cytostatic rather than 
      cytotoxic. As such, these agents are, in general, likely to be administered over 
      long periods of time. Therefore, as well as having proven antitumour efficacy, an 
      anti-angiogenic compound will need to be well-tolerated if it is to become 
      established in the clinical management of patients with malignant disease.
FAU - O'Byrne, K J
AU  - O'Byrne KJ
AD  - University Department of Oncology, Osborne Building, Leicester Royal Infirmary, 
      Infirmary Square, Leicester, LE1 5WW, UK. kobyrne@uhl.trent.nhs.uk
FAU - Steward, W P
AU  - Steward WP
LA  - eng
PT  - Journal Article
PL  - England
TA  - Expert Opin Emerg Drugs
JT  - Expert opinion on emerging drugs
JID - 101135662
EDAT- 2005/07/02 09:00
MHDA- 2005/07/02 09:01
CRDT- 2005/07/02 09:00
PHST- 2005/07/02 09:00 [pubmed]
PHST- 2005/07/02 09:01 [medline]
PHST- 2005/07/02 09:00 [entrez]
AID - 10.1517/14728214.6.1.155 [doi]
PST - ppublish
SO  - Expert Opin Emerg Drugs. 2001 Apr;6(1):155-74. doi: 10.1517/14728214.6.1.155.