Chemocentryx Demonstrates Recently Discovered Chemokine Receptor CXCR7 Is Essential In Tumor Growth
Mountain View, CA - ChemoCentryx, Inc., a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing therapeutics that target the chemokine system, recently 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 recently 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 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.
SOURCE: ChemoCentryx, Inc.