Others inhibit the angiogenesis signaling cascade
- Anti-VEGF antibody - Avastin
- SU5416
- SU6668
- PTK787/ZK 22584
Some block the ability of endothelial cells to break down the extracellular
matrix
- Marimistat
- AG3340 . COL-3
- Neovastat
- BMS-275291
What are the potential advantages of angiogenesis inhibitors?
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- Mild side effects compared to
some cancer drugs, and less
toxicity to most healthy cells
- Tumors do not appear to
develop the same resistance to
angiogenesis inhibitors as the
resistance some tumors develop
to chemotherapy drugs
- Improved outcomes appear to
result from varied combinations
of angiogenesis inhibitors,
chemotherapy, and radiation
- Long-term administration may
result in increased survival
- Potential for preventing, slowing
down, or blocking metastasis
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What are the potential disadvantages of angiogenesis inhibitors?
The main disadvantage of angiogenesis inhibitor therapy is lifelong therapy may
be required. When anti-angiogenic therapy is discontinued, dormant but viable
foci of tumors can regain malignant and metastatic properties.
Also, angiogenesis inhibitors may not address all the proteins and small molecules
that are involved in cell signaling and cancer growth. As a result, this therapy may
provide incomplete and/or temporary inhibition of cancer.
Dosage and associated adverse effects are also problematic with angiogenesis
inhibitors. The original goal of angiogenesis inhibitors was to choke a tumor to
death by killing all of its blood vessels. However, the doses required to accomplish
this are toxic to humans and cause intolerable adverse effects, including harm to
normal blood vessels. Lower doses provide less efficacy than higher doses, and
adverse effects still occur.
Summary
- AI's may not necessarily reduce or eliminate tumors, but instead keep
tumors stable and dependent on the angiogenesis inhibitor.
- Improved outcomes appear to require combination treatments.
- Because angiogenesis is important in wound healing and reproduction it
may cause problems with bleeding, blood clotting, heart function, the
immune system, and the reproductive system.
- High cost
- Short-term efficacy
What is the availability of angiogenesis inhibitors?
Some angiogenesis inhibitors have been approved by the Food and Drug
Administration for specific types of cancer, and are used "off-label" for other
cancers.
- In June 2006, the FDA approved the drug Avastin in combination with
intravenous 5-FU-based chemotherapy for second-line treatment of
patients with metastatic colorectal cancer.
- In October 2006, the FDA approved Avastin in combination with carboplatin
and paclitaxel for the first-line treatment of patients with unresectable,
locally advanced, recurrent or metastatic non-squamous, non-small cell
lung cancer (NSCLC).
- In July 2009, Avastin was approved for the treatment of metastatic renal cell
carcinoma in combination with interferon alpha.
What is the future of angiogenesis inhibitors?
Researchers have answered many questions about angiogenesis, but many
questions still remain. Scientists do not know whether using angiogenesis
inhibitors to treat cancer will trigger unknown side effects, how long treatment will
need to last, or whether tumor cells will find alternative routes for vascularization.
To answer such questions, human clinical trials are currently underway. Future
research will evaluate the following:
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- Angiogenesis inhibitors targeting multiple
proteins and small molecules at the same
time
- New combinations of cancer therapies with
angiogenesis inhibitors
- Understanding other mechanisms involved in
cancer growth associated with angiogenesis
- Types of people with cancer that are more
likely to benefit from specific angiogenesis
inhibitors
- Molecular and cellular characteristics that are
present when angiogenesis inhibitors work
and do not work in people
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