Tigris Pharmaceuticals Presents Results of Breast Cancer Research at AACR
Annual Meeting
BONITA SPRINGS, Fla., April 30 /PRNewswire/ -- Tigris Pharmaceuticals, Inc., a
privately held drug development company, announced that preclinical data were
presented on its novel molecule, AFP-464, during the recent AACR 100th Annual
Meeting 2009 in Denver. "This research represents a significant advancement
in the treatment of Triple Negative Breast Cancer, one of the most aggressive
forms of invasive breast cancer," stated Edmundo Muniz, M.D., Ph.D., President
and Chief Executive Officer of Tigris.
Sponsored by Tigris, the research was led by Angelika Burger, Ph.D., director
of the Translational Research Laboratory at the Barbara Ann Karmanos Cancer
Institute and professor of Pharmacology at Wayne State University School of
Medicine in Detroit. The research found that the luminal (ER-positive) and the
triple negative (ER, PR, and HER-2 negative) breast cancer cell lines with the
basal A gene profile subtype were very sensitive to AFP-464, while the triple
negative cell lines with the basal B subtype were not. However, when the
latter was pre-treated with a histone deacetylase inhibitor, such as the
suberoylanilide hydroxamic acid (SAHA), also known as vorinostat (Zolinza(R),
Merck & Co. Inc.), the cells became very sensitive to AFP-464. The mechanism
in which this is achieved is believed to be the de-silencing of ER expression
by the histone deacetylase inhibitor, followed by CYP1A1 induction and
subsequent AFP metabolism into active species that covalently bind to DNA in
these cancer cells and cause specific cell death.
Dr. Burger said the findings offer particular hope to those women battling
triple-negative breast cancer. "We could now find a way to treat every kind of
invasive, metastatic breast cancer, the ER-positive and ER-negative types with
AFP-464," said Dr. Burger. "The synergism between AFP-464 and vorinostat in
the triple negative breast cancer cell lines is very impressive."
AFP464 is nearing completion of Phase I clinical testing at Jules Bordet
Institute in Belgium, Institut Gustav Roussy in Paris, Mayo Clinic in
Rochester, Minnesota, Karmanos Cancer Institute in Detroit and University of
Maryland Marlene and Stewart Greenebaum Cancer Center in Baltimore. Tigris
Pharmaceuticals expects to soon move to Phase II clinical studies, including
studies in triple-negative breast cancer patients with the drug alone or in
combination with vorinostat, depending on the molecular gene profile subtypes
of the patients. Triple-negative breast cancer afflicts mostly young women
under the age of 40 and is more prevalent in the African-American and Hispanic
community. About 182,460 women in the United States were diagnosed with
invasive breast cancer in 2008, approximately 15-18% of which are triple
negative, and about 40,480 will die from the disease, according to the
American Cancer Society.
"Patients with triple negative breast cancer do not benefit from endocrine
therapy or molecularly targeted therapy such as trastuzumab because they lack
the targets for these drugs," said Dr. Binh Nguyen, M.D., Ph.D., Chief Medical
Officer of Tigris. "The potential of using molecular gene profile to target
the appropriate patient population that most likely could benefit from the
treatment with AFP-464 is the right direction in the clinical development of
this difficult to treat disease."
About AFP-464
AFP-464, a Lysol prodrug of aminoflavone (AF), undergoes rapid conversion to
AF by nonspecific plasma esterases. It has shown a unique pattern of growth
inhibitory activity in the NCI's 60 tumor cell line screen, with breast,
ovarian, lung and renal lines exhibiting particular sensitivity. The
mechanism of action of AF is believed to be that treatment with AF results in
translocation of the arylhydrocarbon receptor (AhR; a transcriptional
regulator of CYP1A1) from the cytoplasm to the nucleus, and its subsequent
interaction with the xenobiotic-response element (XRE) sequence on the CYP1A1
promoter region, causing induction of CYP1A1 transcription. This enzyme
expression converts AF to metabolites that are covalently bound to DNA. This
results in phosphorylation of p53 with induction of the p53 downstream target
p21Waf1/Cip1 and apotosis.
About Tigris Pharmaceuticals, Inc.
Tigris Pharmaceuticals, Inc. is a privately held biopharmaceutical company
that develops therapeutic technologies, using a translational research
approach, for use in oncology and other areas of unmet medical need. Tigris'
mission is to efficiently move its existing and future technologies through
the various stages of clinical development in order to meet patients' needs
for safe and effective treatments of human illnesses.
About the Barbara Ann Karmanos Cancer Institute
Located in mid-town Detroit, Michigan, the Barbara Ann Karmanos Cancer
Institute is one of 40 National Cancer Institute-designated comprehensive
cancer centers in the United States. Caring for more than 6,000 new patients
annually on a budget of $216 million, conducting more than 700 cancer-specific
scientific investigation programs and clinical trials, the Karmanos Cancer
Institute is among the nation's best cancer centers. Through the commitment of
1,000 staff, including nearly 300 faculty members, and supported by thousands
of volunteer and financial donors, the Institute strives to prevent, detect
and eradicate all forms of cancer. For more information call 1-800-KARMANOS or
go to www.karmanos.org.
This news release contains forward-looking statements that involve risks and
uncertainties that could cause our actual results and experiences to differ
materially from anticipated results and expectations expressed in such
forward-looking statement. These forward-looking statements include, without
limitation, statements regarding the mechanism of action of AFP-464, its
potential advantages, its potential for use in treating cancer, as well as the
timing, progress and anticipated results of the clinical development and
regulatory processes concerning AFP-464. These statements are based on our
current beliefs and expectations as to such future outcomes, and are subject
to known and unknown risks and uncertainties that may cause actual future
experience and results to differ materially from the statements made. Factors
that might cause such a material difference include, among others, risks that
the results of clinical trials will not support our claims or beliefs
concerning the effectiveness of AFP-464, our ability to finance our
development of AFP-464, regulatory risks, and our reliance on third party
researchers and other collaborators. We assume no obligation to update these
statements, except as required by law.
SOURCE Tigris Pharmaceuticals, Inc.
Anne White, Chief Operating Officer, Tigris Pharmaceuticals, Inc.,
+1-239-444-5400, info@tigrispharma.com,
