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.