Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
PZ HTL SA
GLOBETECH PUBLISHING LLC

Shutting Down Multiple DNA Synthesis Pathways Cures Leukemia in Mouse Model

By BiotechDaily International staff writers
Posted on 10 Mar 2014
Image: The number of leukemia cells (red) was greatly reduced in treated (right) vs. untreated (left) mice while sparing any significant damage to normal blood cells (black) (Photo courtesy of the Rockefeller University Press).
Image: The number of leukemia cells (red) was greatly reduced in treated (right) vs. untreated (left) mice while sparing any significant damage to normal blood cells (black) (Photo courtesy of the Rockefeller University Press).
Drug treatment that combined inhibitors of both the de novo (DNP) and salvage (NSP) pathways for DNA synthesis cured acute lymphoblastic leukemia (ALL) in a mouse model of the disease.

Investigators at the University of California, Los Angeles (USA) blocked the DNP synthesis of DNA by treating ALL mice with thymidine. This treatment was not sufficient to prevent growth of cancer cells, which switched to the NSP pathway.

To block the NSP pathway the investigators administered DI-39, a new high affinity small-molecule inhibitor of the rate-limiting enzyme DC kinase (DCK). DCK is required for the phosphorylation of several deoxyribonucleosides and their nucleoside analogs. Deficiency of DCK is associated with resistance to antiviral and anticancer chemotherapeutic agents. Conversely, increased DCK activity is associated with increased activation of these compounds to cytotoxic nucleoside triphosphate derivatives. DCK is clinically important because of its relationship to drug resistance and sensitivity.

The investigators reported in the February 24, 2014, online edition of the Journal of Experimental Medicine that a therapeutic regimen that simultaneously co-targeted the DNP pathway with thymidine and the NSP pathway with DI-39 was effective against ALL models in mice, without detectable host toxicity.

"This new dual targeting approach shows that we can overcome the redundancy in DNA synthesis in ALL cells and identifies a potential target for metabolic intervention in ALL, and possibly in other hematological cancers," said senior author Dr. Caius Radu, associate professor of molecular and medical pharmacology at the University of California, Los Angeles. "This interdisciplinary study not only advances our understanding of DNA synthesis in leukemic cells but also identifies targeted metabolic intervention as a new therapeutic approach in ALL. Clinical trials will be required to establish whether these promising findings will translate into a new therapeutic approach for ALL."

Related Links:

University of California, Los Angeles



comments powered by Disqus

Channels

Genomics/Proteomics

view channel

New Program Encourages Wide Distribution of Genomic Data

A new data sharing program allows genomics researchers and practitioners to analyze, visualize, and share raw sequence data for individual patients or across populations straight from a local browser. The sequencing revolution is providing the raw data required to identify the genetic variants underlying rare diseases... Read more

Lab Technologies

view channel

Experimental Physicists Find Clues into How Radiotherapy Kills Cancer Cells

A new discovery in experimental physics has implications for a better determination of the process in which radiotherapy destroys cancer cells. Dr. Jason Greenwood from Queen’s University Belfast (Ireland) Center for Plasma Physics collaborated with scientists from Italy and Spain on the work on electrons, and published... Read more

Business

view channel

Interest in Commercial Applications for Proteomics Continues to Grow

Increasing interest in the field of proteomics has led to a series of agreements between private proteomic companies and academic institutions as well as deals between pharmaceutical companies and novel proteomics innovator biotech companies. Proteomics is the study of the structure and function of proteins.... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.