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Sanford-Burnham scientists unravel cancer drug's secret to resistance
Date:3/19/2012

LA JOLLA, Calif., March 19, 2012 Drug resistance is a serious problem for cancer patientsover time, a therapy that was once providing some benefit simply stops working. Scientists at Sanford-Burnham Medical Research Institute (Sanford-Burnham) recently discovered how cancer cells develop resistance to a drug called MLN4924. This experimental therapy is currently being tested in a number of Phase I and Phase I/II clinical trials to determine its efficacy against several different types of cancer, including multiple myeloma, leukemia, and lymphoma.

Published online March 19 by Cell Reports, the study shows that MLN4924-resistant cancer cells escape death because they have a simple mutation in the drug's targetNEDD8-activating enzymethat prevents the drug from binding. In unraveling this mechanism, the researchers also developed a relatively quick, low-cost laboratory method that can be used to personalize cancer therapies by predicting how cancer patients will respond to this or other drugsall before a person starts taking it.

"Due to genetic variability, some tumors might be more prone to developing resistance to treatment than others. Pinpointing the right treatment for an individual can be a frustrating and costly trial-and-error process. The method we developed in this study to determine the mechanism of resistance for one anti-cancer drug gives us a jumpstart on knowing if this resistance mechanism will hold true for other drugspotentially saving time and money," said Matthew Petroski, Ph.D., assistant professor in Sanford-Burnham's National Cancer Institute-designated Cancer Center and senior author of the study.

MLN4924: Promising anti-cancer drug

MLN4924 kills most cancer cells by binding and inactivating the NEDD8-activating enzyme. NEDD8 and the enzymes that control it are part of the ubiquitin proteasome system (so-named because it's ubiquitous, found in every cell in the body).

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Contact: Heather Buschman, Ph.D.
hbuschman@sanfordburnham.org
858-795-5343
Sanford-Burnham Medical Research Institute
Source:Eurekalert  

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