Bill Dougall

Amgen’s Bill Dougall, scientific director of Oncology Research, has been named one of the “Notable People in R&D” by R&D Directions magazine.  The R&D Directions article profiles the accomplishments of Dougall and his team in researching denosumab in oncology. Read the article below.*

The Hunt for Cancer’s Achilles’ Heel

For many people living with breast, lung, prostate, and other cancers, the spread of the disease to the bones can be the most painful part. When tumors invade bone, they can make them weaker, resulting in skeletal complications such as fractures or spinal cord compression, which frequently require surgery or radiation treatment. For oncology scientists such as Bill Dougall, Ph.D., finding a way to help patients by intervening in bone metastases – or perhaps even stopping cancer from reaching the skeleton – is a chief motivation behind their research.

“It’s really important for patients that we try to intercede in both of these areas,” says Dr. Dougall, scientific director of oncology research at biotechnology company Amgen Inc. (amgen.com). “It would be a huge advance in medicine and the treatment of cancer.”

According to Amgen, an estimated 70% to 80% of patients with advanced breast cancer, for example, develop bone metastases.

Dr. Dougall and his team of 10 Amgen scientists have been searching for a vulnerability in cancer-induced bone disease – something that can be targeted with a drug. Those efforts may soon pay off. In the last few years, Dr. Dougall’s department has watched its research go from the hypothesis stage to the full-blown development of a potential novel therapy, denosumab. The human monoclonal antibody is the first and only therapy in late-stage development that specifically neutralizes RANK Ligand, the essential regulator of osteoclasts, which are the cells that break down bone. Denosumab has been studied in 7,000 clinical-trial patients in the oncology setting, and more Phase III data is expected to be released in 2010. Dr. Dougall’s team is actively supporting regulatory filings for denosumab in advanced cancer this year.

The drug, administered as a twice-yearly subcutaneous injection, has already been filed with FDA for the treatment of osteoporosis in post-menopausal women. Amgen is awaiting formal feedback from the agency in this indication.

Dr. Dougall, who works at Amgen’s Seattle, Wash., research site, has spent most of the last two decades building on the discoveries that spawned denosumab and advancing that understanding in the oncology and bone biology settings.

“There’s something to be said for trusting the science, diving in, and following it into a new area that might have a clinical application,” he says.

A key turning point in the denosumab project was an early discovery made by Dr. Dougall’s lab at what was then Immunex Corp. The company merged with Amgen in 2002. Dr. Dougall was part of the research team that identified the novel protein RANK and its corresponding RANK Ligand. Meanwhile, a group of Amgen scientists, working independently, identified, cloned, and determined the function of osteoprotegerin, or OPG, a cytokine which can inhibit the production of osteoclasts.

The Immunex and Amgen teams then published the seminal papers elucidating the OPG/RANK/RANK Ligand pathway, which is now recognized as the central pathway regulating osteoclasts. Further research of the pathway led to the development of denosumab. Today, Dr. Dougall leads Amgen’s preclinical research efforts to develop the product in oncology.

“What’s really important for patients is that we’ve learned over the last couple of years that there is a role for RANK Ligand and osteoclastic activity in osteoblastic disease,” Dr. Dougall says. “The hope has been that there’s one key factor that drives cancer-induced bone disease, and that it’s applicable in many different tumor types and many different kinds of bone lesions that result from metastasis.”

Dr. Dougall says his earlier career aspirations did not include being a cancer researcher. His first love was marine biology, but by the time the Jacksonville, Fla., native began college at the University of Florida at Gainesville, his interests expanded to include cell biology and molecular biology.

* Posted with permission from R&D Directions, Feb. 2010.