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Experimental insulin-like growth factor receptor inhibitor reduced pancreatic cancer growth

Researchers at Amgen are testing a fully human monoclonal antibody that inhibits the activity of insulin-like growth factors (IGF-1 and IGF-2) and appears to reduce pancreatic cancer cells in early testing, according to a report in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research.

Pancreatic cancer is one of the deadliest cancers, and less than 4 percent of the 200,000 patients diagnosed annually live more than five years. The only available clinical treatment is gemcitabine, but this has yet to show a survival benefit.

Scientists are testing a variety of experimental therapies to bring pancreatic cancer under control. At Amgen, Pedro J. Beltran, Ph.D., a principal scientist in oncology research, is experimenting with AMG 479, a fully human anti-IGF-1 monoclonal antibody.

"We know that insulin-like growth factors play a role in cancer development, particularly in mediating cell survival. This is the first drug that specifically targets the receptor for these growth factors without cross-reacting with the closely related insulin receptor," said Beltran.

In the in vitro study, AMG 479 bound to IGF-1R and blocked both IGF-1 and IGF-2 binding factors 1 and 2. It also completely inhibited ligand-induced activation in some growth factors, which led to a decreased cellular viability. When Beltram and colleagues measured the effect of AMG 479 on pancreatic cancer cells in vivo, the inhibition rate was approximately 80 percent inhibition of tumor growth and receptor expression was observed.

"These data clearly show that AMG 479 is a clinical candidate for pancreatic cancer therapy, either alone or in combination with gemcitabine," he said.

Beltran said researchers are currently testing AMG 479 in nine separate phase II studies of various cancer types; he expects the effect will be seen beyond pancreatic cancer.

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 more than 28,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and 80 other countries. The 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. The AACR publishes six major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Jeremy Moore | EurekAlert!
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