Marshall Edwards' Phenoxodiol and Novogen's NV-128 Display Divergent Mechanisms of Action but Potent Synergistic Anti-Cancer Act
October 30 2008 - 7:18PM
Marketwired
Pre-clinical studies presented at the 9th International Conference
on Membrane Redox Systems in Wellington New Zealand this week
demonstrate that Novogen's NV-128 (a novel mTOR inhibitor), when
used in combination with the Marshall Edwards, Inc.'s Phase III
anti-ovarian cancer drug, phenoxodiol, produces potent synergistic
anti-cancer activity against non-small cell lung carcinoma cell
lines (NSCLC). Importantly, the synergistic cytotoxicity observed
between NV-128 and phenoxodiol was superior to the synergy observed
between NV-128 and paclitaxel against NSCLC. These data were
presented by Dr. David Brown, Program Manager (Cancer Biology),
Novogen.
"In NSCLC targets, these two drugs in combination produced an
anti-cancer effect superior to that achieved with either drug alone
or in combination with current approved anti-cancer cytotoxic
drugs. The potential for improved efficacy, coupled with the safety
profile of these novel drugs, suggests the potential for clinical
benefits in lung cancer patients which cannot be achieved with
current standard of care drugs," Dr. Brown said.
Phenoxodiol is being developed as a therapy for late-stage,
chemoresistant prostate and ovarian cancers. It is a novel-acting
drug that inhibits key pro-survival signaling pathways operating
via sphingosine-1-phosphate and Akt. Inhibition of these pathways
leads to prevention of phosphorylation of key anti-apoptotic
proteins such as XIAP and FLIPs. Loss of activity of these proteins
restores the ability of chemoresistant tumor cells to undergo
caspase-mediated apoptosis in response to chemotherapy. The
putative molecular target for phenoxodiol is a surface oxidase
which is preferentially expressed on cancer cells and is linked to
the expression of pro-survival pathways in these cells. The ability
of the drug to bind preferentially to cancer cells rather than
normal cells is reflected in its high safety profile in clinical
use.
In contrast to phenoxodiol, NV-128 does not induce
caspase-mediated apoptosis, a death mechanism which is often
non-functional in chemoresistant cancer cells due to accumulated
mutations in tumor suppressor/promoter genes and over-expression of
anti-apoptotic proteins. Rather, NV-128 uncouples the
akt-mTOR-P70S6K signal transduction cascade which has a key role in
driving protein translation and uncontrolled cancer cell
proliferation. Further, NV-128 induces mitochondrial depolarization
via a novel pathway involving the autophagy protein Beclin-1 and
Bcl-2, thereby resulting in endonuclease G translocation to the
nucleus and cell death. Importantly, when NV-128 is used in
combination with phenoxodiol, XIAP is degraded in these cells
allowing the caspase-mediated apoptosis cascade to be engaged in
addition to NV-128-endonuclease G mediated apoptosis resulting in
two pathways to cell death.
"These data provide direct evidence that while invoking discrete
modes of cell death, NV-128 and phenoxodiol can be used
synergistically to force the convergence of caspase-mediated and
caspase-independent cell death pathways to drive overall cell
death," said Dr. Brown.
About Novogen Limited:
Novogen Limited (ASX: NRT) (NASDAQ: NVGN) is an Australian
biotechnology company that has patented isoflavone technology for
the treatment and prevention of degenerative diseases and
disorders. Over the past ten years, Novogen has conducted the
largest and most comprehensive isoflavone clinical testing programs
in the world. Novogen is involved in drug discovery and product
development for a range of degenerative disorders including cancer,
cardiovascular diseases and inflammatory diseases. The Company
coordinates an international clinical research and development
program with external collaborators, hospitals and universities.
For more information, visit www.novogen.com.
About Marshall Edwards, Inc:
Marshall Edwards, Inc. (NASDAQ: MSHL) is majority owned by
Novogen. It as a specialist oncology company focused on the
clinical development of novel anti-cancer therapeutics derived from
the flavonoid technology platform. This platform has generated a
number of novel anti-cancer compounds characterized by broad
ranging activity against a range of cancer cell types with few side
effects. The combination of anti-tumor cell activity and low
toxicity is believed to be a result of the ability of these
compounds to target an enzyme present on the surface of cancer
cells, thereby inhibiting the production of pro-survival proteins
within the cell. Marshall Edwards, Inc. has licensed rights from
Novogen Limited (NASDAQ: NVGN) to bring three oncology drugs --
phenoxodiol, triphendiol and NV-143 -- to market globally. The
Company's lead investigational drug, phenoxodiol, is in a Phase III
multinational multi-centered clinical trial for patients with
recurrent ovarian cancer. More information on the trial can be
found at http://www.OVATUREtrial.com.
Under U.S. law, a new drug cannot be marketed until it has been
investigated in clinical trials and approved by the FDA as being
safe and effective for the intended use. Statements included in
this press release that are not historical in nature are
"forward-looking statements" within the meaning of the "safe
harbor" provisions of the Private Securities Litigation Reform Act
of 1995. You should be aware that our actual results could differ
materially from those contained in the forward-looking statements,
which are based on management's current expectations and are
subject to a number of risks and uncertainties, including, but not
limited to, our failure to successfully commercialize our product
candidates; costs and delays in the development and/or FDA
approval, or the failure to obtain such approval, of our product
candidates; uncertainties in clinical trial results; our inability
to maintain or enter into, and the risks resulting from our
dependence upon, collaboration or contractual arrangements
necessary for the development, manufacture, commercialization,
marketing, sales and distribution of any products; competitive
factors; our inability to protect our patents or proprietary rights
and obtain necessary rights to third party patents and intellectual
property to operate our business; our inability to operate our
business without infringing the patents and proprietary rights of
others; general economic conditions; the failure of any products to
gain market acceptance; our inability to obtain any additional
required financing; technological changes; government regulation;
changes in industry practice; and one-time events. We do not intend
to update any of these factors or to publicly announce the results
of any revisions to these forward-looking statements.
Add to Digg Bookmark with del.icio.us Add to Newsvine
Contacts: David Sheon 202 422-6999 Email Contact Christopher
Naughton 011 61 2 9878 0088 Email Contact
Kazia Therapeutics (NASDAQ:KZIA)
Historical Stock Chart
From Jun 2024 to Jul 2024
Kazia Therapeutics (NASDAQ:KZIA)
Historical Stock Chart
From Jul 2023 to Jul 2024