Meet the Investigator – Dr. Matthew Smith

Men receiving androgen deprivation therapy for prostate cancer may be at risk for osteoporosis and bone fractures. Recent published reports which highlight the work of PCF-funded researcher Dr. Matthew Smith have shown promising results in reducing this occurrence through the development of a promising new drug named denosumab.

Bone loss and fractures can be a painful complication for men undergoing androgen deprivation therapy to treat prostate cancer.  They are associated with loss of height, curvature of the spine, and decreased quality and length of life.

At the Massachusetts General Hospital Cancer Center, PCF-funded researcher Dr. Matthew Smith has worked to improve the health of prostate cancer survivors and helped lead the development of denosumab, a novel new drug that targets and inactivates osteoclasts – the cells responsible for bone loss.

“Fractures adversely impact the lives of men who have been treated for prostate cancer” said Dr. Smith, lead investigator of the Denosumab HALT Prostate Cancer Study Group.  “But fractures are a a preventable problem. The results of this study may have an important impact on the care of many thousands of prostate cancer survivors.”

In the three-year trial study, twice-yearly injection of denosumab markedly increased bone mineral density at all monitored sites including the hip and spine. Importantly, denosumab also decreased spine fractures by 62 percent.  The study, conducted at 156 institutions throughout the U.S. and Europe, included 1,468 men who were undergoing androgen deprivation therapy for prostate cancer.

Denosumab works by targeting the rank ligand (RANKL) pathway, a critical signaling protein that regulates bone remodeling.   Androgen deprivation therapy results in excess RANKL activity leading to bone loss and fractures.

“What the PCF has done is to support, in a very timely way, high return yet potentially high risk research projects,” said. Dr. Smith. “When I proposed this original research in 1997 to look at this issue of fractures, there was really no other funding agencies interested due to the absence of preliminary data.  The PCF helped to fund this innovative work and just a decade later, we’re looking at the completion of a trial that we believe may change the future of clinical practice.”

On September 26, Dr. Smith will present his findings to his colleagues in prostate cancer research at the PCF’s annual Scientific Retreat held in Lake Tahoe, Nevada. 

In its sixteenth year of existence, the retreat brings together the world’s leading prostate cancer researchers in an effort to break down the traditional barriers that impede progress toward better treatments and a cure for prostate cancer.

With more than 200 scientific leaders from academia, governmental agencies and the biopharmaceutical industry at the retreat, Dr. Smith welcomes the opportunity to share his work with others in the field.

“It’s the event of the year in prostate cancer,” explains Dr. Smith. “I’m always excited to attend the retreat because it's an extraordinary opportunity to collaborate with colleagues from many different disciplines who are deeply committed to prostate cancer research.  There is nothing comparable to it in the field.”

In October of this year, shortly after the Scientific Retreat, Dr. Smith hopes to recieve the FDA’s approval for denosumab. The drug, which has been recommended by the FDA approval committee, is also currently being studied for its effectiveness in blocking bone metastasis in prostate cancer patients.

“My hope is that the results from this trial will lead to a new therapeutic option to prevent fractures for men receiving androgen deprivation,” said Dr. Smith. “I’m also excited about continued studies of denosumab where we’re looking to treat and prevent bone metastasis in prostate cancer. There’s a lot more to come to this story.”