Abstract
The discovery of endogenous inhibitors of angiogenesis has made it possible to test the hypothesis that blocking the angiogenic switch may keep tumor growth in check, and has added a new investigational arm to the field of cancer gene therapy. Angiogenesis inhibitors are heterogeneous in origin and potency, and their growing list includes proteolysis products of larger molecules with a different function, such as angiostatin, endostatin and vasostatin, modulators of vascular endothelial growth factor activity, such as sFLT-1, and some cytokines/chemokines with marked anti-endothelial activity, such as IL-12, IFN-α, and CXCL10. Pre-clinical studies have clearly indicated that these factors are essentially cytostatic and that they need long-term administration in order to obtain prolonged anti-tumor effects, representing a rational basis for their delivery by a gene therapy approach. The experimental approaches attempted to date, reviewed herein, indicate overall that anti-angiogenic gene therapy has efficacy mainly as an early intervention strategy and that a better understanding of the biological mechanisms underlying resistance to angiogenesis inhibition, as well as appropriate combined treatments, are required to generate a conceptual advancement which could drive the field towards successful management of established tumors.
| Original language | English |
|---|---|
| Pages (from-to) | 87-114 |
| Number of pages | 28 |
| Journal | Molecular Aspects of Medicine |
| Volume | 28 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Feb 2007 |
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Keywords
- Angiogenesis
- Angiostatin
- Cancer
- Endostatin
- Gene therapy
- Interferon
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Molecular Medicine
Cite this
Anti-angiogenic gene therapy of cancer : Current status and future prospects. / Persano, Luca; Crescenzi, Marika; Indraccolo, Stefano.
In: Molecular Aspects of Medicine, Vol. 28, No. 1, 02.2007, p. 87-114.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anti-angiogenic gene therapy of cancer
T2 - Current status and future prospects
AU - Persano, Luca
AU - Crescenzi, Marika
AU - Indraccolo, Stefano
PY - 2007/2
Y1 - 2007/2
N2 - The discovery of endogenous inhibitors of angiogenesis has made it possible to test the hypothesis that blocking the angiogenic switch may keep tumor growth in check, and has added a new investigational arm to the field of cancer gene therapy. Angiogenesis inhibitors are heterogeneous in origin and potency, and their growing list includes proteolysis products of larger molecules with a different function, such as angiostatin, endostatin and vasostatin, modulators of vascular endothelial growth factor activity, such as sFLT-1, and some cytokines/chemokines with marked anti-endothelial activity, such as IL-12, IFN-α, and CXCL10. Pre-clinical studies have clearly indicated that these factors are essentially cytostatic and that they need long-term administration in order to obtain prolonged anti-tumor effects, representing a rational basis for their delivery by a gene therapy approach. The experimental approaches attempted to date, reviewed herein, indicate overall that anti-angiogenic gene therapy has efficacy mainly as an early intervention strategy and that a better understanding of the biological mechanisms underlying resistance to angiogenesis inhibition, as well as appropriate combined treatments, are required to generate a conceptual advancement which could drive the field towards successful management of established tumors.
AB - The discovery of endogenous inhibitors of angiogenesis has made it possible to test the hypothesis that blocking the angiogenic switch may keep tumor growth in check, and has added a new investigational arm to the field of cancer gene therapy. Angiogenesis inhibitors are heterogeneous in origin and potency, and their growing list includes proteolysis products of larger molecules with a different function, such as angiostatin, endostatin and vasostatin, modulators of vascular endothelial growth factor activity, such as sFLT-1, and some cytokines/chemokines with marked anti-endothelial activity, such as IL-12, IFN-α, and CXCL10. Pre-clinical studies have clearly indicated that these factors are essentially cytostatic and that they need long-term administration in order to obtain prolonged anti-tumor effects, representing a rational basis for their delivery by a gene therapy approach. The experimental approaches attempted to date, reviewed herein, indicate overall that anti-angiogenic gene therapy has efficacy mainly as an early intervention strategy and that a better understanding of the biological mechanisms underlying resistance to angiogenesis inhibition, as well as appropriate combined treatments, are required to generate a conceptual advancement which could drive the field towards successful management of established tumors.
KW - Angiogenesis
KW - Angiostatin
KW - Cancer
KW - Endostatin
KW - Gene therapy
KW - Interferon
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UR - http://www.scopus.com/inward/citedby.url?scp=33847247850&partnerID=8YFLogxK
U2 - 10.1016/j.mam.2006.12.005
DO - 10.1016/j.mam.2006.12.005
M3 - Article
C2 - 17306361
AN - SCOPUS:33847247850
VL - 28
SP - 87
EP - 114
JO - Molecular Aspects of Medicine
JF - Molecular Aspects of Medicine
SN - 0098-2997
IS - 1
ER -