Oncology News Updates
Curis Announces Nature Publication on Paracrine Mechanism of Action in Hedgehog-Expressing Tumors
Curis News Release
Aug 27, 2008
Curis, Inc., a drug development company focused on developing next generation proprietary targeted medicines for cancer treatment, today announced the publication of preclinical data in
Nature that support the premise that Hedgehog proteins play an important role in supporting tumor growth in Hedgehog-expressing solid tumors through a paracrine mechanism of action.
The paper reported that analysis of human tissue samples by Genentech scientists revealed that subsets of colorectal, endometrial, ovarian and pancreatic cancers overexpressed Hedgehog protein. The paper also included data on preclinical pancreatic and colon cancer xenograft models demonstrating that administration of a Hedgehog antagonist results in significant growth delay of the underlying tumor.
"This paper reports compelling evidence of paracrine signaling and the tumor growth inhibitory effects of Hedgehog antagonists. These data suggest that Hedgehog antagonists may have therapeutic value not just in cancers driven by mutations in the Hedgehog signaling pathway, such as basal cell carcinomas (BCC), but also potentially in cancers where Hedgehog signaling is driven by overexpression of the Hedgehog protein," said Dan Passeri, Curis' President and CEO. "We are encouraged by our collaborator Genentech's decision to conduct Phase II trials of GDC-0449 in colorectal and ovarian cancer, in addition to a study in metastatic and locally advanced BCC. We believe that the insights provided by these studies into the underlying mechanisms of Hedgehog's involvement in cancer may lead to more effective treatment regimens using Hedgehog antagonists such as GDC-0449."
In the paracrine setting, the Hedgehog protein is expressed by the tumor cells but has its biologic effect upon the surrounding supporting cells (stromal cells), including effecting these surrounding cells to support growth of the Hedgehog-secreting tumor cells. Genentech is currently conducting clinical testing of GDC-0449. In May 2008, Genentech initiated a Phase II clinical trial in which approximately 150 patients with colorectal cancer will be treated with chemotherapy in combination with bevacizumab and will be randomized to receive GDC-0449 or placebo. In addition, Genentech has indicated that it expects to initiate Phase II testing of GDC-0449 in advanced ovarian cancer during the second half of 2008.
Phase I investigators have presented encouraging efficacy and safety data on the treatment of advanced basal cell carcinoma patients with GDC-0449 during the American Association for Cancer Research (AACR) Annual Meeting in April 2008 (Abstract #LB-138) and the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2008 (Abstract #3516). The data presented at AACR included the achievement of clinical benefit (clinical or radiological responses or prolonged stable disease) in 8 of 9 patients treated with GDC-0449. No dose-limiting adverse events occurred. Two cases of reversible drug-related Grade 3 hyponatremia (lowered serum sodium level) and one case of reversible Grade 3 drug-related fatigue were the only grade 3 events reported as of the data cutoff date of April 1, 2008. Genentech has indicated that it expects to initiate a Phase II advanced basal cell carcinoma clinical trial during the second half of 2008.
Return to Oncology News Updates