SAN DIEGO, Aug. 15, 2002 (PRIMEZONE) -- Scientists from McGill University and Angstrom Pharmaceuticals Inc., (San Diego, CA) published preclinical results on the combination therapy of its drug A6 with tamoxifen (TAM), a hormonal drug widely used by patients with malignant breast cancer. The study is featured in today's issue of Cancer Research, a leading peer-reviewed journal.
The study, entitled "An Antiangiogenic Urokinase-derived Peptide Combined with Tamoxifen Decreases Tumor Growth and Metastasis in a Syngeneic Model of Breast Cancer," evaluated the effects of A6 and the antiestrogen TAM alone and in combination on estrogen-receptor-positive Mat B-III rat breast cancer cells in vitro and in vivo. In the in vivo experiments, the Mat B-III orthotopic tumors, formed from cells inoculated in the mammary fat pad, were staged to 30-40 mm3 before starting therapy with A6 (75 mg kg/day) and/or tamoxifen (3 mg/kg/day). Therapy was continued for 17 days during which time the animals were evaluated for primary tumor growth. A6 or tamoxifen alone each inhibited tumor growth by 50% and A6, but not tamoxifen, reduced the number of macroscopic metastatic tumor foci. In contrast, the combination of A6 and tamoxifen led to significantly greater (75%) inhibition of tumor growth than observed with either agent alone. In addition to inhibitions of tumor growth, there was a decrease in new blood-vessel density and increased tumor cell death; these effects were more pronounced in the A6 + TAM combination treatment.
Follow-on in vitro experiments conducted with Mat B-III cells to provide a molecular basis for these in vivo effects showed that both TGF-beta activity and vascular endothelial growth factor receptor Flk-1 protein level were substantially reduced. Each of these is an important factor contributing to tumor progression. A6 alone reduced TGF-beta activity to 65% of control while A6 plus tamoxifen reduced it further to 40%. A6 alone reduced Flk-1 protein level to 45% of control while A6 plus tamoxifen reduced it further to 35%. The Flk-1 results are noteworthy because the human counterpart to Flk-1 is VEGFR2, a receptor targeted by several of Angstrom's competitors.
A6 is a proprietary new, non-toxic, antiangiogenic, and antimetastatic drug that Angstrom has developed. It is a small molecule drawn from the structure of urokinase plasminogen activator (uPA), a key molecule involved in tumor angiogenesis and tumor metastasis. uPA is found at the invasive edge of virtually all solid tumors including breast, prostate, colon, and lung, but is rarely found in normal tissue. A6 interferes with the activity of the uPA system and is currently being prepared for clinical trials, the first of which is expected to take place at the end of this year.
"This study indicates that combining a novel antiangiogenic/antimetastatic agent, A6, with hormone therapy can enhance the anti-tumor effects of hormone therapy through increased inhibition of angiogenesis and induction of tumor cell death," said Shafaat A. Rabbani, M.D., Principal Investigator at McGill. Terence R. Jones, Ph.D., Founder and Chief Technical Officer of Angstrom added "Our colleagues at McGill have previously shown that A6 as a monotherapy has dramatic effects on tumor growth and metastasis in a model of estrogen-independent human breast cancer in nude mice. The results of these two studies have potential implications for both prophylaxis as well as treatment of early stage breast cancer in the clinical setting."
Angstrom Pharmaceuticals (www.angstrominc.com) is a development-stage pharmaceutical company in San Diego which recently completed the first close of its first round of venture financing led by HamiltonApex Technology Ventures (www.hamiltonapexventures.com). The company has chosen cancer and ophthalmology as its first focus and currently has several active antiangiogenesis programs in these areas.
When used in this report, the words "expects" and similar expressions are intended to identify forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements are subject to risks and uncertainties, which could cause actual results to differ materially from those projected, anticipated, or implied.
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