WASHINGTON, DC – A new way to help the body absorb and retain the most active form of vitamin D (calcitriol) holds promise for cancer patients. Scientists from the laboratory of Candace Johnson, PhD, Senior Vice President for Translational Research, and Donald Trump, MD, Senior Vice President for Clinical Research, Roswell Park Cancer Institute (RPCI), will present their research at the 97^th Annual Meeting of the American Association for Cancer Research, April 1-5, in the Washington Convention Center, Washington, DC*. 

The RPCI study shows that systemic exposure to calcitriol, the most active form of vitamin D3, can be enhanced when administered in combination with inhibitors of CYP24 activity. Calcitriol has demonstrated powerful growth inhibitory effects in preclinical models of human cancers and therapeutic efficacy in patients with prostate cancer non-responsive to hormonal therapy. However, the high serum calcitriol levels required to inhibit cancer growth are not reproducibly achieved in patients. One possible explanation is inter-patient differences in the metabolic inactivation of calcitriol. 24-hydroxylase (CYP24) is the major vitamin D₃ inactivating enzyme; RC2204 and ketoconazole are inhibitors of CYP24.

Researchers, under the direction of Josephia Muindi, MD, PhD, investigated whether higher and longer duration of exposure could be achieved when calcitriol was administered in combination with an inhibitor of 24-hydroxylase activity. To test this hypothesis, normal mice were treated with calcitriol alone or calcitriol in combination with either ketoconazole or RC2204. Blood calcitriol levels were measured at various times after treatment.

Researchers observed a 30% increase in systemic calcitriol exposure in mice treated with calcitriol + ketoconazole, compared with mice treated with calcitriol alone. The increase in systemic calcitriol exposure was four times higher in the calcitriol + RC2204 group than in the group treated with calcitriol alone. Studies are in progress to evaluate the use of CYP24 inhibitors to enhance therapeutic efficacy of vitamin D₃-based therapies in patients with a variety of advanced cancers.

          Founded in 1907, the American Association for Cancer Research is the world’s oldest and largest professional organization dedicated to advancing cancer research. Members include more than 24,000 basic, translational and clinical researchers, health care professionals, and cancer survivors and advocates in the United States and in more than 60 other countries.

Roswell Park Cancer Institute, founded in 1898, is the nation’s first cancer research, treatment, and education center and is the only National Cancer Institute-designated comprehensive cancer center in Upstate New York. RPCI is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers. For more information, visit RPCI’s website at www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email askrpci@roswellpark.org

*Editor’s Note: (Abstract # 2153) “Inhibitors of 24-Hydroxylase Activity Enhance Systemic Calcitriol Exposure in Preclinical Animal Models” Embargoed until Monday, April 3, 8 am - Noon

Exhibit Hall, Washington Convention Center, Poster Session 16: Novel Preclinical Combinations.