Special Project Angiogenesis

Angiostatic Approach to Cancer Therapy


Various inhibitors of angiogenesis are under investigation in patients with advanced cancer:
Drugs that block matrix breakdown:
Drug Sponsor Trial Mechanism
Marimastat British Biotech; Annapolis, MD Phase III against pancreas, non-small cell lung, breast cancers Synthetic inhibitor of matrix metalloproteinases (MMPs) 
Bay 12-9566 Bayer; West Haven, CT Phase III against lung, ovary, and pancreatic cancers Synthetic inhibitor of tumor growth
AG3340 Agouron; LaJolla, CA Phase III against non-small cell lung; phase III against prostate cancer Synthetic MMP inhibitor
CGS 27023A Novartis; East Hanover, NJ Phase I/II Synthetic MMP inhibitor
COL-3 Collagenex; Newtown, PA/NCI Phase I Synthetic MMP inihibitor. Tetracycline® derivative
Neovastat Aeterna; Sainte-Foy, Québec Phase III against non-small cell lung cancer (will open in 1999) Naturally occurring MMP inhibitor
BMS-275291 Bristol-Myers Squibb; Wallingford, CT Phase I Synthetic MMP inhibitor

Drugs that inhibit endothelial cells directly:
Drug Sponsor Trial Mechanism
TNP-470 TAP Pharmaceuticals, Deerfield, IL Phase II against advanced cancer for adults with solid tumors; Phase I against pediatric solid tumors, lymphomas, and acute leukemias Synthetic analogue of fumagillin; inhibits endothelial cell growth
Thalidomide Celgene; Warren, NJ Phase II against Kaposi's sarcoma, glioblastoma, prostate, lung, and breast cancers Unknown
Squalamine Magainin Pharmaceuticals; Plymouth Meeting, PA Phase I Extract from dogfish shark liver; inhibits sodium-hydrogen exchanger, NHE3
Combretastatin A-4 (CA4P) Oxigene; Boston, MA Phase I; Phase II to begin late 1999  Induction of apoptosis in proliferating endothelial cells
Endostatin EntreMed; Rockville, MD Phase I solid tumor study to begin later in 1999  Inhibition of endothelial cells

Drugs that block activators of angiogenesis:
Drug Sponsor Trial Mechanism
Anti-VEGF Antibody Genentech; South San Francisco, CA Phase II/III against lung, breast, prostate, colorectal, and renal cancers Monoclonal antibody to vascular endothelial growth factor (VEGF)
SU5416 Sugen; South San Francisco, CA Phase I/II against Kaposi's sarcoma, Phase I/II against metastatic colorectal cancer, and Phase I/II against advanced malignancies Blocks VEGF receptor signaling
SU6668  Sugen; South San Francisco, CA Phase I against advanced tumors Blocks VEGF, FGF, and EGF receptor signaling
PTK787/ZK 22584 Novartis; East Hanover, NJ Phase I against advanced cancers (Germany and UK); Phase I against glioblastoma and Kaposi's sarcoma; Phase I/II against Von Hippel Lindau disease  Blocks VEGF receptor signaling
Interferon-alpha Commercially Available Phase II/III Inhibition of bFGF and VEGF production

Drugs that inhibit endothelial-specific integrin/survival signaling:
Drug Sponsor Trial Mechanism
Vitaxin Ixsys; La Jolla, CA Phase II enrollment will begin in 1999 Antibody to integrin present on endothelial cell surface
EMD121974 Merck KCgaA; Darmstadt, Germany Phase I/II against Kaposi's sarcoma, brain tumors, and solid tumors (to open in 1999) Small molecule blocker of integrin present on endothelial cell surface

Drugs with non-specific mechanism of action:
Drug Sponsor Trial Mechanism
CAI NCI; Bethesda, MD Phase II/III against ovarian, non-small cell lung, and renal cell cancers Inhibitor of calcium influx
Interleukin-12 Genetics Institute; Cambridge, MA Phase I/II against Kaposi's sarcoma and solid tumors Up-regulation of interferon gamma and IP-10
IM862 Cytran; Kirkland, WA Phase III against AIDS-related Kaposi's sarcoma Unknown mechanism

Even though no definitive conclusions can be drawn, antiangiogenic therapy combined with conventional anticancer therapies may represent an useful tool in the future care of patients with cancer.

Click here for a list of clinical trials in progress with angiogenesis inhibitors.

For more and updated informations take a look at Anti-Angiogenesis NCI Clinical Trials web page.

Questions about anti-angiogenesis therapy? Click here.

Quantitation of microvessel density in tumor specimens has been perfomed. The evaluation of blood vessel density in a tumor may help to predict the risk of metastases or recurrence. Recent observations have confirmed this hypothesis for different types of tumors, including breast cancer.