Die aktuelle und zukünftige antiangiogene Therapie zielt bevorzugt auf das Zytokin
VEGF (Vascular Endothelial Growth Factor) ab, entweder sehr spezifisch über Antikörper
oder Peptide, die VEGF oder seine Rezeptoren blockieren, oder weniger spezifisch über
Rezeptor-Tyrosinkinaseinhibitoren (RTKI), die neben den VEGF-Rezeptoren zusätzlich
immer auch andere, mit ihnen verwandte Tyrosinkinasen hemmen. Das therapeutische Potenzial
von VEGF und anderen angiogenen Mediatoren wie Sphingosin 1-phosphat bzw. ihren Rezeptoren
ist aber bei weitem noch nicht voll ausgeschöpft. Zusätzlich bieten die direkte Beeinflussung
der Tumorvaskulatur durch „Vascular Disrupting Agents“ und die natürlichen Hemmer
der Angiogenese, Angiostatin und Endostatin, weitere Angriffspunkte. Auch durch eine
besondere Applikationsweise („metronomisch“) kann eine Chemotherapie antiangiogene
Wirkung entfalten.
Vascular Endothelial Growth Factor (VEGF) and its receptors represent the main target
of the antiangiogenic therapy to date and in the future, either by specific blocking
antibodies and peptides, or by receptor tyrosine kinase inhibitors (RTKI). RTKIs are
less specific and also inhibit other related tyrosine kinases. However, the therapeutical
potential of VEGF and other angiogenic mediators such as sphingosine 1-phosphate and
their receptors is far from being exhausted. In addition, “Vascular Disrupting Agents”
that target the established tumor vasculature and natural inhibitors of angiogenesis
(angiostatin and endostatin) offer new treatment options. Also chemotherapy itself,
when administered in a particular, “metronomic” schedule, can have antiangiogenic
properties.
Key words
VEGF - monoclonal antibodies - receptor tyrosine kinase inhibitors - sphingosine 1-phosphate
- vascular disrupting agents - endostatin
Literatur
- 1
Hsu JY, Wakelee HA..
Monoclonal antibodies targeting vascular endothelial growth factor: current status
and future challenges in cancer therapy.
Bio Drugs.
2009;
23
289-304
- 2
Ma J, Waxman DJ..
Combination of antiangiogenesis with chemotherapy for more effective cancer treatment.
Mol Cancer Ther.
2008;
7
3670-3684
- 3
Chu QS..
Aflibercept (AVE0005): an alternative strategy for inhibiting tumour angiogenesis
by vascular endothelial growth factors.
Expert Opin Biol Ther.
2009;
9
263-271
- 4
Mross K, Stefanic M, Gmehling D et al..
Phase I study of the angiogenesis inhibitor BIBF 1120 in patients with advanced solid
tumors.
Clin Cancer Res.
2010;
16
311-319
- 5
De Boer R, Arrieta O, Gottfried M et al..
Vandetanib plus pemetrexed versus pemetrexed as second-line therapy in patients with
advanced non-small cell lung cancer (NSCLC): A randomized, double-blind phase III
trial (ZEAL).
J Clin Oncol.
2009;
27
- 6
Friedrich FW, Eschenhagen T..
Fingolimod – a new immunomodulator.
Dtsch Med Wochenschr.
2009;
134
2127-2131
- 7
Gridelli C, Rossi A, Maione P et al..
Vascular disrupting agents: a novel mechanism of action in the battle against non-small
cell lung cancer.
Oncologist.
2009;
14
612-620
- 8
O'Reilly MS, Holmgren L, Shing Y et al..
Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases
by a Lewis lung carcinoma.
Cell.
1994;
79
315-328
- 9
Sun Y, Wang J, Liu Y et al..
Results of phase III trial of rh-endostatin (YH-16) in advanced non-small cell lung
cancer (NSCLC) patients.
J Clin Oncol.
2005;
23
- 10
Lin X, Huang H, Li S et al..
A phase I clinical trial of an adenovirus-mediated endostatin gene (E10A) in patients
with solid tumors.
Cancer Biol Ther.
2007;
6
648-653
- 11
Cavazzana-Calvo M, Thrasher A, Mavilio F..
The future of gene therapy.
Nature.
2004;
427
779-781
- 12
Gasparini G..
Metronomic scheduling: the future of chemotherapy?.
Lancet Oncol.
2001;
2
733-740
Korrespondenz
Prof. Dr. med. Robert Möhle
Medizinische Klinik II Abteilung für Onkologie, Hämatologie, Immunologie, Rheumatologie
und Pulmologie Universitätsklinikum Tübingen
Otfried-Müller-Straße 10
72076 Tübingen
Fax: 07071/293179
eMail: robert.moehle@med.uni-tuebingen.de