American Association for Cancer Research

Press Releases: 2008

New Molecule Shows Promise in Patients with Advanced Basal Cell Carcinoma


April 14, 2008

SAN DIEGO - A novel molecule, GDC-0449, shrinks tumors for patients with advanced basal cell carcinoma with limited side effects, suggesting a viable new treatment option for patients with the advanced form of this cancer, according to research presented at the 2008 Annual Meeting of the American Association for Cancer Research.

"Basal cell carcinoma affects about one million people a year, and a very small fraction of these patients have disease that is not curable with surgery. We currently do not have any treatments that can effectively slow tumor growth in these advanced patients. This finding has enormous implications in this population," said Daniel D. Von Hoff, M.D., physician in chief at the Translational Genomics Research Institute (TGen) and chief medical officer for the Scottsdale Clinical Research Institute at Scottsdale Healthcare in Arizona.

GDC-0449 works by inhibiting the Hedgehog pathway. The Hedgehog ligands are a family of proteins that are important in tissue growth and repair. The ligands signal via two cell surface receptors called PTCH and SMO. Abnormal activation of Hedgehog signaling pathway because of mutations in PTCH and SMO is the cause of most basal cell carcinomas.

Von Hoff presented data from a phase I trial conducted at Scottsdale Healthcare, Karmanos Cancer Institute at Wayne State University, and the Sidney Kimmel Cancer Center at Johns Hopkins. This trial tested GDC-0449 in humans for the first time. Researchers enrolled nine patients with advanced basal cell carcinoma. Patients received oral doses of GDC-0449 once a day continuously.

Durable clinical benefit, defined as tumor stabilization or shrinkage visible on X-ray or other physical exam, was observed in eight of patients evaluated, and lasted a median of over 176 days. The first patient treated in the trial has shown clinical improvement for over 438 days, Von Hoff says, with mild side effects. "He came to us short of breath and in pain, but he has had a very dramatic response with this drug," Von Hoff said.

Of the original nine patients, two have had shrinkage of their tumors as measured by computerized tomography (CT) scans, four have had shrinkage or improvement of their tumors by clinical exam, two have had prolonged periods without tumor growth, and one has had significant tumor growth.

Further evaluations of the study participants measured the presence of GLI1, a genetic marker of Hedgehog pathway activity, in skin cells sampled from the participants. Among all patients tested to date, there was a reduction in this marker, indicating that the drug was affecting the Hedgehog pathway.

"The drug has been extremely well tolerated. Some patients lose a sense of taste, and there has been a small amount of hair loss and weight loss, but the toxicity has been mild," Von Hoff said.

Efficacy data of GDC-0449, a systemic Hedgehog pathway antagonist, in a first-in-human, first-in-class Phase I study with locally advanced, multifocal or metastatic basal cell carcinoma patients: Abstract LB-138

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The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 27,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is the only journal worldwide dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.