Microarray Analysis and Preclinical Treatment Model
Reveal Extensive Activity of Decoy Aptamers
BERKELEY HEIGHTS, NJ November 26, 2002
- Genta Incorporated (Nasdaq: GNTA) announced the presentation and
publication of new data that show broad genomic and preclinical
anticancer activity of one of the Company's key pipeline products,
the CRE-decoy aptamer. The results were presented at the "
Molecular Targets and Cancer Therapeutics
" symposium in Frankfurt, Germany, which was jointly sponsored by
the American Association for Cancer Research (AACR), the European
Organization for the Treatment of Cancer (EORTC), and the U.S.
National Cancer Institute (NCI).
A region of DNA, known as the cyclic AMP response
element (CRE), regulates the function of a number of genes that are
critically involved in cancer cell growth and division. These genes
are activated when a complex of proteins (known as transcription
factors) bind to this region of DNA. In collaboration with Genta,
researchers at NCI have developed a DNA-based medicine called the
"CRE-decoy aptamer". This drug binds to and blocks the protein
complexes that would normally turn on genes regulated by CRE,
thereby inhibiting cancer cell growth. Recent studies have shown
that this approach is selective for cancer cells without harming
normal cells.
The current study is an extension of prior research
that broadly examined the effects of Genta's CRE-decoy aptamer on
more than 1,000 human genes, using a process known as DNA
microarray analysis. When compared with control decoys and normal
liver cells, tumor cells treated with the CRE-decoy showed marked
activation of genes that were known to be involved in cancer cell
development, growth, and differentiation.
The most significant activity was observed in
hormone-resistant breast cancer cells. Based on this analysis, a
preclinical model of human breast cancer was then tested in
animals, and the anticancer activity of the CRE-decoy was compared
with tamoxifen, a standard drug used for the treatment of patients
with breast cancer. The CRE-decoy proved markedly superior to
tamoxifen in a dose-related manner. Complete results have been
published in the current issue of the
Proceedings of the National Academy of Science (USA)
, which can be viewed at the following link:
http://www.pnas.org/cgi/content/abstract/242617799v1maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=cho,+y&searchid=1037909955614_6645&stored_search=&FIRSTINDEX=0
"This work is a key extension of our ongoing
program with aptamer technology, which addresses a central
regulatory gene involved in cancer growth", commented Dr. Raymond
P. Warrell, Jr., Genta's Chief Executive Officer. "We have
identified specific lead compounds from this important pipeline
program, and we look forward to advancing them into late-stage
preclinical testing that will determine their suitability for entry
into clinical trials." Genta has a Cooperative Research and
Development Agreement (CRADA) with NCI that supports this work.
