Abstract
Introduction
Antiangiogenic drugs represent a new class of antitumor therapeutics that will
be used along with cytotoxic agents, targeted agents, and immunomodulatory
agents to fi ght cancer. The fi rst antiangiogenic compound on the market,
Genentech' s Avastin (bevacizumab), has become one of the top-selling
anticancer drugs worldwide. In November 2007, another antiangiogenic agent,
Onyx/Bayer' s Nexavar, became the fi rst agent approved to treat hepatocellular
carcinoma. Based on Avastin' s success, pharmaceutical and biotechnology
companies are developing a rich pipeline of antiangiogenic agents, including
multitargeted kinase inhibitors, other smallmolecule compounds, and
large-molecule biological agents.
Get the Answers You Need to Shape Your Strategy
- The vascular endothelial growth factor (VEGF) pathway is the most well
understood of the angiogenic pathways and all approved antiangiogenic
drugs--Avastin, Onyx/Bayer' s Nexavar (sorafenib), and Pfi zer' s Sutent
(sunitinib)- primarily target this pathway and its receptors. What other
pathways are associated with angiogenesis? What are the disadvantages of
targeting the VEGF pathway? What pathways do emerging antiangiogenic drugs
target?
- Current antiangiogenic agents offer only limited benefi t to patients in
terms of improved survival and quality of life. How have emerging
antiangiogenic compounds fared in clinical trials? What strategies are drug
developers exploring to improve the effi cacy of antiangiogenic drugs?
- Resistance to anti-VEGF agents remains a challenge to the long-term effi
cacy of existing anti-angiogenic agents. What approaches are pharmaceutical
companies taking to address VEGF resistance? Does the targeting of HIF
(hypoxia-inducible factor) or mTOR (mammalian target of rapamycin) represent a
viable strategy to overcoming VEGF resistance?
Scope
- Tumor angiogenesis: the systems that contribute to its growth and
those that inhibit its growth.
- Marketed antiangiogenic agents: Genentech' s Avastin (bevacizumab),
Onyx/Bayer' s Nexavar (sorafenib), and Pfi zer' s Sutent (sunitinib).
- Emerging antiangiogenic agents: Adnexus' s Angiocept, Amgen' s
AMG-386, AstraZeneca' s cediranib, AstraZeneca' s Zactima, Celgene' s thalidomide
derivatives, GlaxoSmithKline' s pazopanib, MedImmune' s abegrin, Merck KGaA' s
cilengitide, Novartis' s vatalanib, PDL BioPharma/Biogen Idec' s volociximab,
Pfi zer' s axitinib, Regeneron/Sanofi -Aventis' s afl ibercept, UCB/ImClone' s
CDP-791.
- Strategies to improve antiangiogenic agents: maximizing the effi
cacy of antiangiogenic compounds and preventing development of resistance to
the compounds.
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