Anti-angiogenesis therapies: their potential in cancer management

Figures & data

Table 1 Features of tumor vasculature compared to normal blood vessels⁸

Increased vessel tortuosity

Vessels thin walled and fragile

Increased interstitial pressure within tumor

Vessel marker immaturity

Increased vessel permeability

Variable flow rates

Lack of vascular smooth muscle

Constant remodeling

Table 2 Current phase III randomized controlled trials of VEGF tyrosine kinase inhibitors

Drug	Indication
Axitinib (AG-013736)	First-line or second-line therapy for metastatic renal cell cancer First-line therapy for locally advanced, unresectable or metastatic pancreatic cancer (in combination with gemcitabine)
BIBF 1120	First-line therapy for ovarian cancer (in combination with paclitaxel and carboplatin) Second-line therapy for advanced NSCLC (in combination with docetaxel) Second-line therapy for advanced NSCLC (in combination with pemetrexed)
Brivanib alaninate (BMS-540215)	Adjuvant treatment following trans-arterial chemo-embolization (TACE) for hepatocellular carcinoma First-line treatment of hepatocellular carcinoma Second-line treatment of hepatocellular carcinoma Following irinotecan and oxaliplatin for metastatic colorectal cancer (in combination with cetuximab)
Cediranib (AZD2171)	First-line treatment of metastatic colorectal cancer (in combination with oxaliplatin and a fluoropyrimidine) Recurrent glioblastoma (alone and in combination with lomustine) First-line therapy of advanced NSCLC Relapsed ovarian epithelial, fallopian tube or primary peritoneal cancer (in combination with carboplatin and paclitaxel)
Pazopanib (GW786034)	Ovarian, fallopian tube or primary peritoneal cancer (immediately after first-line chemotherapy) Relapsed or progressive inflammatory breast cancer (in combination with lapatinib) First-line therapy for locally advanced or metastatic renal cell carcinoma Relapsed or progressive metastatic soft tissue sarcoma Adjuvant therapy in stage I NSCLC
Motasenib (AMG 706)	Advanced NSCLC (in combination with paclitaxel and carboplatin)
Semaxinib (SU5416)	First-line therapy for metastatic colorectal cancer (in combination with leucovorin and 5-fluorouracil) First-line therapy for metastatic colorectal cancer (in combination with leucovorin, 5-fluorouracil and irinotecan)
Sorafenib (BAY 43-9006)	Multiple trials in hepatocellular carcinoma, renal cell cancer, melanoma, pancreatic cancer, NSCLC, differentiated thyroid cancer
Sunitinib (SU11248)	Multiple trials in renal cell carcinoma, GIST, breast cancer, pancreatic cancer, NSCLC, colorectal cancer
Vandetanib (AZD6474)	Second-line therapy for NSCLC (in combination with pemetrexed) Second-line therapy for NSCLC (in combination with docetaxel) Second-line therapy for NSCLC Following failure of EGFR TKI in NSCLC
Vatalanib (PTK787/ZK222584)	First-line therapy for metastatic colorectal cancer (in combination with leucovorin, 5-fluorouracil and oxaliplatin) Irinotecan-resistant metastatic colorectal cancer (in combination with leucovorin, 5-fluorouracil and oxaliplatin)

Notes: All data from clinicaltrials.gov, accessed December 13, 2009.

Abbreviations: EGFR, epidermal growth factor receptor; GIST, gastro-intestinal stromal tumor; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor.

Table 3 Examples of biological vascular disrupting agents⁸⁹

Agent	Mechanism of action
Anti-endoglin-ricin A	Antibody bound to a toxin
Anti-TES-23-neocarzinostatin	Antibody bound to a cytotoxic agent
Anti-VCAM-1-tissue factor	Antibody bound to tissue factor (induces intravascular thrombosis)
L19 scFv-IL-12	Antibody bound to a cytokine
L19 scFv-TNFα	Antibody bound to a cytokine
VEGF-gelonin	Growth factor bound to a plant toxin

Abbreviations: IL, interleukin; TES, tissue endothelium specific; TNF, tumor necrosis factor; scFv, single chain variable fragment; VCAM, vascular cell adhesion molecule; VEGF, vascular endothelial growth factor.

KakolyrisSFoxSBKoukourakisMRelationship of vascular maturation in breast cancer blood vessels to vascular density and metastasis, assessed by expression of a novel basement membrane component, LH39Br J Cancer200082484485110732757

 PubMed Web of Science ®Google Scholar

ThorpePEChaplinDJBlakeyDCThe first international conference on vascular targeting: meeting overviewCancer Res20036351144114712615734

 PubMedGoogle Scholar