Hedgehog Pathway Implicated in Human Pancreatic Carcinoma and other Cancers
Monday September 15, 8:43 am ET
Two Reports in the Journal Nature Also Confirm Efficacy of Hedgehog Inhibitors in Blocking Tumor Growth in Cancer Models
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Sept. 15, 2003-- Curis, Inc. (NASDAQ:CRIS - News) today announced that the current online issue of the scientific journal Nature contains two reports demonstrating a linkage between the malignant growth of certain tumors, including high mortality pancreatic carcinoma, and abnormal expression of the Hedgehog signaling pathway. These reports also show that inhibition of the Hedgehog pathway is effective in blocking the growth of these tumors in models of cancer treatment. In June, Curis established a cancer therapeutic partnership based on Hedgehog pathway inhibition with Genentech, Inc. (NYSE:DNA - News), a biotechnology company based in South San Francisco, California.
The first Nature report demonstrates that abnormal expression of the Hedgehog pathway occurs not only in established pancreatic cancer but also in the precursor lesions from which pancreatic cancer is believed to arise. Treatment of pancreatic tumor cell lines with cyclopamine, a compound known to inhibit the Hedgehog pathway, is able to block tumor growth in preclinical cancer models. The authors conclude that identification of Hedgehog's role in initiation and maintenance of pancreatic cancer "may hold promise for new diagnostic and therapeutic approaches" for this devastating disease. This report, entitled "Hedgehog is an Early and Late Mediator of Pancreatic Cancer Tumorigenesis," is from the laboratories of Dr. Matthias Hebrock at the University of California, San Francisco, and Dr. Sarah Thayer at the Massachusetts General Hospital and the Harvard Medical School.
The other Nature publication is from Dr. Philip Beachy and his colleagues at the Johns Hopkins University School of Medicine and is entitled "Widespread Requirement for Hedgehog Ligand Stimulation in Growth of Digestive Tract Tumors." These investigators report that a wide range of digestive tract tumors, including the majority of those originating from esophagus, stomach, biliary tract, and pancreas display abnormal levels of Hedgehog pathway activity. In their experiments, treatment with cyclopamine results in tumor regression in cancer growth models. The authors conclude that tumors abnormally expressing the Hedgehog pathway "may respond to antagonist- or antibody-mediated pathway blockage, even in advanced stages of metastatic disease."
The Hedgehog signaling pathway is one of the major regulatory mechanisms used by the body for the development and maintenance of tissues and organs. One of its biological properties is to promote the expression of various tissue growth factors, including factors that control the growth of blood vessels (angiogenesis factors).
"Several years ago, we developed the hypothesis that certain cancers may be using the Hedgehog pathway as a means of providing tumors with growth factor support and that inhibitors of the Hedgehog pathway may constitute a novel and selective approach for the treatment of these cancers," said Dr. Lee Rubin, Curis' Chief Scientific Officer. "Since then, several cancers, including basal cell carcinoma, medulloblastoma, small cell lung cancer, and now these additional cancers, have been linked to abnormal expression of the Hedgehog pathway. Curis has successfully developed several promising Hedgehog inhibition drug candidates, including small molecule Hedgehog antagonists and a Hedgehog antibody, that are effective in blocking tumor growth in cancer models. These two new reports in Nature add substantially to our understanding of the tumor biology associated with abnormal expression of the Hedgehog pathway."
Daniel Passeri, Curis' President and Chief Executive Officer stated, "Pancreatic carcinoma is one of the deadliest forms of cancer and there is no adequate therapy. Of the approximate 30,000 new cases each year in the United States, 95% will die within five years. These reports in Nature provide some of the strongest evidence yet that inhibition of the Hedgehog pathway constitutes an important drug development approach to the treatment of these cancers. Our partnership with Genentech, to develop new cancer therapies based on Hedgehog pathway inhibition, now has a greatly expanded array of oncology clinical targets."
About Curis, Inc.
Curis, Inc. is a therapeutic drug development company. The Company's technology focus is on regulatory pathways that control repair and regeneration. Curis' product development involves the use of proteins or small molecules to modulate these pathways. Curis has successfully used this technology and product development approach to produce several promising drug product candidates in the fields of kidney disease, neurological disorders, cancer, and alopecia (hair loss). For more information, please visit the Curis web site at www.curis.com. |
