Discovery and Development of Antiangiogenetic Drugs in Ovarian Cancer
Pp. 191-215 (25)
Madon M. Maile, Evelyn Y. T. Wong, Daphne Suzin, Nicole E. Birrer and Richard T. Penson
It is more than 30 years since the seminal observations by Folkman of the
development of new blood vessels (angiogenesis) in tumors. Ovarian cancer remains the
most lethal gynecologic malignancy in the US, and angiogenesis is a particularly
important target as VEGF levels are high, manifest as ascites and pleural effusions, and
the response rates to single agent bevacizumab, a recombinant humanized monoclonal
antibody directed against VEGF, are the highest (16-25%) of any reported in oncology.
Antiangiogenics have generally been well tolerated, but are associated with
gastrointestinal perforation in 1-2%. New angiogenesis targets are being identified
(ANG-2, PDGFR, FGFR, inflammation and the microenvironment), and a plethora of
new agents is in clinical development: tyrosine-kinase inhibitors (sunitinib, cediranib,
pazopanib), multitargeted agents (XL-184), anti-angiopoietins (trebananib), novel antivascular
approaches (VB-111 and ombrabulin). Antiangiogenic therapy appears to
impact PFS, but does not impact cure. In subsets of patients, it may improve overall
survival (OS), and its use remains costly and controversial. Although approved in
Europe, the pathway to approval of bevacizumab for ovarian cancer in the US is
currently still unclear. There is a clinical need to define the role of these drugs in
ovarian cancer management and to identify robust predictive biomarkers.
Aflibercept, angiogenesis, bevacizumab, blood, cediranib, disruption,
dormancy, endothelium, factor, inhibitor, kinase, maintenance, normalization,
novel, pazopanib, progression, remission, survival, trebananib, tyrosine, vascular,
Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, Mailstop: Yawkey 9064, USA.