WASHINGTON, DC – Take the “gold standard” chemotherapy drug regimen for colorectal cancer, add a new investigational drug to the mix and you may offer a more effective formula for enhancing the treatment’s ability to kill tumor cells in this disease, according to scientists from the laboratories of Lakshmi Pendyala, PhD, Department of Medicine, and Carl W. Porter, PhD, Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute (RPCI). Their research will be presented at the 97^th Annual Meeting of the American Association for Cancer Research, April 1-5, in the Washington Convention Center, Washington, DC.*

Their study showed that the use of diethylnorpsermine (DENSPM) in conjunction with oxaliplatin and 5-fluorouracil (5FU) increases polyamine catabolism in colon carcinoma cells. Oxaliplatin and 5FU are used together to treat colorectal cancer. Combining DENSPM with oxaliplatin and 5FU in a colon carcinoma cell line significantly increased the activities of enzymes ­– spermine/spermidine N¹-acetyltransferase (SSAT) and spermine oxidase (SMO) – that break down polyamines, small positively charged molecules known to be essential for cancer cell growth.

Earlier studies in the Porter laboratory indicated that SSAT and SMO induction and/or depletion of polyamines causes tumor cell kill. Thus, the enzyme effect seen with this drug combination may have clinical significance. This belief is supported by the additional finding that expression of enzyme mRNA is increased in tumor biopsies from patients treated with oxaliplatin-based therapy.

The investigators conclude that drugs such as oxaliplatin and 5FU can be effectively combined with a clinically relevant polyamine analog, DENSPM, to enhance the conversion of enzyme mRNA to active protein and thus, increase antitumor activity. Current studies are evaluating the drug combination in human tumor models growing in mice and optimizing the conditions for a potential future clinical application.

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 # 3831 “Effect of oxaliplatin (Oxp), 5-fluorouracil (5FU) and N1, N11 diethylnorspermine (DENSPM) on polyamine catabolism in colon carcinoma cells”

Embargoed until Tuesday, April 4, 8am

Exhibit Hall, Washington Convention Center, Poster Session 32: Targeting Multiple Levels in Molecular Therapeutics.