Characterization of Receptor's Central Role in Cancer is Published in the
Proceedings of the National Academy of Sciences
MOUNTAIN VIEW, Calif., Sept. 26 /PRNewswire/ -- ChemoCentryx, Inc., a
clinical-stage biopharmaceutical company focused on discovering, developing
and commercializing therapeutics that target the chemokine system, today
announced the publication of data from a series of rigorous experiments to
elucidate CXCR7's essential role in the progression and development of
certain cancers. CXCR7 is a novel chemokine receptor whose function was
discovered and characterized by ChemoCentryx.
ChemoCentryx scientists, joined by researchers from the University of
Michigan and the Iowa State University, found that CXCR7 plays a crucial
role in both tumor development and progression by enabling cancer cell
survival and promoting the process of angiogenesis (the growth of new blood
vessels). Importantly, CXCR7 can be readily detected on many primary human
tumor tissue samples (such as breast and lung cancers), but CXCR7 is not
expressed by surrounding healthy tissue. Findings from the company's
research are presented in an article titled "CXCR7 promotes breast and lung
tumor growth in vivo and is expressed on tumor-associated vasculature" in
the September 26, 2007 Early Edition and October 2, 2007 print edition of
the Proceedings of the National Academy of Sciences (PNAS).
"Our labs were thrilled to have the opportunity to collaborate in
support of ChemoCentryx's ground-breaking research on CXCR7," said Gary D.
Luker, M.D., Assistant Professor, Department of Radiology, Department of
Microbiology and Immunology, University of Michigan Medical School. "With
broad implications of targeting CXCR7 for cancer treatment, this work
exemplifies how great science, done well, may lead directly to the
discovery and development of new medicines."
"These data represent a significant scientific finding with potentially
profound clinical implications, providing the first demonstration that
CXCR7 -- which was discovered as well as characterized by ChemoCentryx
using our proprietary EnabaLink Drug Discovery engine -- is fundamental to
cancer growth and progression and therefore, an important new cancer
target," said Thomas J. Schall, Ph.D., ChemoCentryx's President and Chief
Executive Officer.
Evidence of a Causal Connection between CXCR7 and Tumor Growth and
Progression
In a series of carefully controlled experiments, a causal connection
was identified between the presence and expression of the CXCR7 gene and
tumor progression in breast and lung cancer models. In these experiments,
ChemoCentryx scientists were able to clearly demonstrate the effect in vivo
of up- and down-regulation of CXCR7, and how that controlled tumor growth.
Isolating the CXCR7 receptor from potential interference by other chemokine
receptors (such as the related receptor known as CXCR4), researchers
demonstrated that CXCR7 cells formed significantly larger tumors in breast
and lung cancer models. These findings extend research previously reported
in the September 4, 2006 edition of The Journal of Experimental Medicine,
showing that the introduction of CXCR7 into cell lines resulted in the
avoidance of apoptosis, or programmed cell death, a hallmark of the
uncontrolled cell proliferation associated with cancer. Further, in
knockout experiments in which the CXCR7 gene was down-regulated, tumor
growth was significantly impaired, thus showing that CXCR7 was required for
the ability of tumors to grow well in vivo. CXCR7 expression was also
observed to enhance the ability of breast cancer cells to seed and
proliferate to lung tissue (metastasize) in another cancer model.
These findings appear to be clinically relevant for human cancer. The
study also showed a comprehensive evaluation of over a hundred primary
human breast tumor and lung tumor tissue samples removed by surgery where
the presence of CXCR7 was assessed by antibodies that react specifically
with CXCR7. The analyses of the human tumors verified that CXCR7 is highly
expressed by both the malignant tumor cells and by the tumor-associated
blood vessels in the tumor mass, but not found on healthy cells or normal
vasculature outside of the tumor mass. These findings were further extended
to multiple tumor types, and researchers believe that CXCR7's activity in
cancer may be important in a broad range of malignancies. Observations
around CXCR7's role in tumor vasculature formation were further evidenced
in knockout experiments in a zebrafish model, strongly suggesting that
CXCR7 is central to the formation of new blood vessels during development
(a process known to resemble aspects of new blood vessel formation in
tumors). Taken together, these observations show that CXCR7 may be central
to the rapid formation of new blood vessels, a process known as
angiogenesis, necessary for tumor growth.
"Drugs targeting tumor angiogenesis represent an important mode of
therapy in modern cancer treatment regimens," said Dr. Schall. "Our work
shows that CXCR7 may provide an entirely new and powerful target in the
approach to future oncology therapy."
EnabaLink Identifies Potent Classes of Chemokine-Based Therapeutics
The data published today result from ChemoCentryx's extensive chemokine
drug discovery capabilities and insights into chemokine system biology.
CXCR7 is a chemokine receptor that was 'deorphanized' (a function was
discovered for the protein encoded by a gene of previously unknown
function) at ChemoCentryx through the company's proprietary EnabaLink Drug
Discovery(R) engine. Leveraging the EnabaLink suite of technologies,
ChemoCentryx is uniquely able to identify highly specific product
candidates including orally-active small molecules that bind with high
affinity to a specific chemokine receptor. ChemoCentryx has leveraged its
EnabaLink Drug Discovery engine for the identification and optimization of
each of its clinical and preclinical product candidates. The company is
currently evaluating promising inhibitors of CXCR7 in preclinical studies.
About ChemoCentryx
ChemoCentryx, Inc. is a clinical-stage biopharmaceutical company
focused on discovering, developing and commercializing orally-administered
therapeutics that target the chemokine and chemoattractant systems in order
to treat autoimmune diseases, inflammatory disorders and cancer. The
chemokine system is a complex network of chemokine molecules, or ligands,
and receptors that regulates inflammation. Based on their proprietary drug
discovery and drug development platform, ChemoCentryx has internally
generated several clinical and preclinical-stage programs, each targeting
distinct chemokine and chemoattractant receptors with different small
molecule compounds. ChemoCentryx's lead compound, Traficet-EN(R), a
specific CCR9 antagonist, is currently in a multi-national clinical trial,
called PROTECT-1, in patients with moderate-to-severe Crohn's disease.
ChemoCentryx is privately held. For more information, please refer to
http://www.chemocentryx.com.
Any statements in this press release about ChemoCentryx's expectations,
beliefs, plans, objectives, assumptions or future events or performance are
not historical facts and are forward-looking statements. These statements
are often, but not always, made through the use of words or phrases such as
believe, will, expect, anticipate, estimate, intend, plan and would.
Forward-looking statements are not guarantees of performance. They involve
known and unknown risks, uncertainties and assumptions that may cause
actual results, levels of activity, performance or achievements to differ
materially from any results, levels of activity, performance or
achievements expressed or implied by any forward-looking statement. Some of
the risks, uncertainties and assumptions that could cause actual results to
differ materially from estimates or projections contained in the
forward-looking statements include but are not limited to (i) the timing,
success and cost of preclinical research and clinical studies, (ii) the
timing, acceptability and review periods for regulatory filings, (iii) the
availability of corporate partners, (iv) uncertainties relating to patent
protection and intellectual property rights of third parties, (v) the
impact of competitive products and technological changes, (vi) the
availability of capital and the cost of capital, (vii) other vagaries in
the biotechnology industry and (viii) other risks. ChemoCentryx undertakes
no obligation to update or revise any forward-looking statements.
SOURCE ChemoCentryx, Inc.
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Related links:
http://www.chemocentryx.com
CONTACT:
Susan M. Kanaya, Senior Vice President,
Finance and Chief Financial Officer, or Markus J. Cappel, Ph.D.,
Chief Business Officer, both of ChemoCentryx, Inc.,
+1-650-210-2900, investor@chemocentryx.com; or media, Karen L.
Bergman, +1-650-575-1509, or Michelle Corral, +1-415-794-8662,
both of BCC Partners, for ChemoCentryx, Inc.
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