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Blogger's Note: this is not an open access journal
Author Affiliations
- Correspondence to: Rakesh K. Jain, PhD, Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom St, Cox 734, Boston, MA 02114 (e-mail: jain@steele.mgh.harvard.edu).
Angiogenesis (the term referring generically to new blood vessel formation) is a hallmark of all solid tumors (1), and vascular endothelial growth factor (VEGF) is the most prevalent and potent angiogenic growth factor in these tumors
(2,3).
For this reason, there have been intense efforts to develop therapies
that target the VEGF pathway. Currently, there are
nine antiangiogenic drugs approved by the US Food
and Drug Administration and one pending approval (Table 1) (4).
These agents are antibodies that target VEGF itself (bevacizumab and
aflibercept) or its receptor VEGFR2 (ramucirumab),
or are tyrosine kinase inhibitors that interfere
with VEGFR2 signaling as well as other receptor and cellular kinases.
Introduction
of these new drugs over the last decade has
established antiangiogenic therapy as a novel therapeutic modality, but
their
implementation has raised several important
questions. Why do they work in some cancers and not others? Is the
mechanism of
action similar when targeting the ligand versus the
receptors, or when using specific versus multitargeted drugs? Can any
of them completely block the VEGF pathway? What
mediates the inevitable escape from therapy? Can we find biomarkers to
identify
patients who will benefit from these agents or
pathways that must be targeted when tumors become refractory to a given
antiangiogenic
agent?
Table 1.
Overview of successful phase III trials of antiangiogenic agents*
Most cancer cell–targeted
drugs target identifiable oncogenic pathways known to drive
tumorigenesis and have corresponding
biomarkers related to those pathways that help
guide treatment. However, the theoretical advantage of antiangiogenic
therapy
over these cancer cell–targeted …
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