Mechanisms of adverse effects of anti-VEGF therapy for cancer

被引:766
作者
Kamba, T.
McDonald, D. M.
机构
[1] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA
[4] Kyoto Univ, Dept Urol, Sakyo Ku, Kyoto 6068507, Japan
关键词
angiogenesis inhibitors; VEGF signalling; capillaries;
D O I
10.1038/sj.bjc.6603813
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Advances in understanding the role of vascular endothelial growth factor (VEGF) in normal physiology are giving insight into the basis of adverse effects attributed to the use of VEGF inhibitors in clinical oncology. These effects are typically downstream consequences of suppression of cellular signalling pathways important in the regulation and maintenance of the microvasculature. Downregulation of these pathways in normal organs can lead to vascular disturbances and even regression of blood vessels, which could be intensified by concurrent pathological conditions. These changes are generally manageable and pose less risk than the tumours being treated, but they highlight the properties shared by tumour vessels and the vasculature of normal organs.
引用
收藏
页码:1788 / 1795
页数:8
相关论文
共 45 条
[1]   Reversible posterior leukoencephalopathy syndrome after bevacizumab/FOLFIRI regimen for metastatic colon cancer [J].
Allen, Jeffrey A. ;
Adlakha, Ashish ;
Bergethon, Peter R. .
ARCHIVES OF NEUROLOGY, 2006, 63 (10) :1475-1478
[2]   Angiopoietin-1 decreases plasma leakage by reducing number and size of endothelial gaps in venules [J].
Baffert, F ;
Le, T ;
Thurston, G ;
McDonald, DM .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2006, 290 (01) :H107-H118
[3]   Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling [J].
Baffert, F ;
Le, T ;
Sennino, B ;
Thurston, G ;
Kuo, CJ ;
Hu-Lowe, D ;
McDonald, DM .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2006, 290 (02) :H547-H559
[4]   Age-related changes in vascular endothelial growth factor dependency and angiopoietin-1 - Induced plasticity of adult blood vessels [J].
Baffert, F ;
Thurston, G ;
Rochon-Duck, M ;
Le, T ;
Brekken, R ;
McDonald, DM .
CIRCULATION RESEARCH, 2004, 94 (07) :984-992
[5]   The Role of Vascular Endothelial Growth Factor in Wound Healing [J].
Bao, Philip ;
Kodra, Arber ;
Tomic-Canic, Marjana ;
Golinko, Michael S. ;
Ehrlich, H. Paul ;
Brem, Harold .
JOURNAL OF SURGICAL RESEARCH, 2009, 153 (02) :347-358
[6]   Sunitinib: From rational design to clinical efficacy [J].
Chow, Laura Q. M. ;
Eckhardt, S. Gail .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (07) :884-896
[7]   Chemotherapy induced reversible posterior leukoencephalopathy syndrome [J].
Connolly, Roisin M. ;
Doherty, Colin P. ;
Beddy, Peter ;
O'Bryne, Ken .
LUNG CANCER, 2007, 56 (03) :459-463
[8]   Rat liver sinusoidal endothelial cell phenotype is maintained by paracrine and autocrine regulation [J].
DeLeve, LD ;
Wang, XD ;
Hu, LP ;
McCuskey, MK ;
McCuskey, RS .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2004, 287 (04) :G757-G763
[9]   Phase 3, multicenter, randomized, double-blind, placebo-controlled trial of SU11248 in patients (pts) following failure of imatinib for metastatic GIST [J].
Demetri, GD ;
van Oosterom, AT ;
Blackstein, M ;
Garrett, C ;
Shah, M ;
Heinrich, M ;
McArthur, G ;
Judson, I ;
Baum, CM ;
Casali, PG .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (16) :308S-308S
[10]   Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases [J].
Eremina, V ;
Sood, M ;
Haigh, J ;
Nagy, A ;
Lajoie, G ;
Ferrara, N ;
Gerber, HP ;
Kikkawa, Y ;
Miner, JH ;
Quaggin, SE .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (05) :707-716