DEC 22, 2015 04:03 PM PST

New Scripps Florida Compound Successfully Targets Hard-to-Treat Breast Cancer

Findings from a new study led by scientists from the Florida campus of The Scripps Research Institute (TSRI) suggest a potent new therapeutic approach for a number of hard-to-treat breast cancers.

The study points to an enzyme called casein kinase 1δ (CK1δ), a critical regulator of growth, as a novel and highly vulnerable therapeutic target. Increased CK1δ expression is common to breast cancer, including the difficult-to-treat subtype called “triple negative breast cancer” (those cancers not driven by estrogen, progesterone, or the HER-2/neu gene), affecting 10 to 20 percent of breast cancer patients.

The study, which was published today in the journal Science Translational Medicine, was a collaboration among the Florida labs of Derek Duckett and William R. Roush, both of TSRI, and John Cleveland, formerly of TSRI and currently at the Moffitt Cancer Center.

“Our findings confirm that aberrant CK1δ regulation promotes tumor growth in breast cancers by activating the protein β-catenin,” said Duckett, an associate professor at Scripps Florida. “The best news, however, is that we have been able to treat CK1δ-expressing breast cancers with a highly selective and potent CK1δ inhibitor developed by Bill Roush’s lab that triggers rapid tumor cell death.”
 
Breast Cancer Cells

At the beginning of the study, the team knew that the β-catenin protein was an oncogene in many cancers, but it was unclear why it was activated in these breast cancer types since they lacked typical mutations in those pathways. The researchers suspected the link could be overexpression of CK1δ. Their experiments showed that indeed to be the case.

To confirm the new target, the study used the Roush lab compound, called SR-3029. SR-3029 was remarkably successful at blocking the growth of tumors in both animal models and in studies with tumor tissue from breast cancer patients.

“SR-3029 removes β-catenin from cancer cells, killing the tumors,” explained Duckett. “This is an extraordinarily promising strategy for targeted treatment with SR-3029, especially in breast cancers that lack targeted treatment options.”
Scripps Florida's Associate Professor Derek Duckett led the collaborative study.
“These results are just the tip of the iceberg,” added Roush, who is professor, associate dean and executive director of medicinal chemistry at TSRI. “Inhibitors such as SR-3029 are being studied in a host of different cancers, and we are hopeful this platform can be translated into clinical applications.”

The first author of the study, “Therapeutic Targeting of Casein Kinase 1δ in Breast Cancer,” is Laura H. Rosenberg, a TSRI research associate at the time of the study. In addition to Rosenberg, Duckett, Roush and Cleveland, other authors include Marie Lafitte, Victor Quereda, Wayne Grant, Weimin Chen, Mathieu Bibian, Yoshihiko Noguchi and Mohammad Fallahi of TSRI; Chunying Yang of Moffitt Cancer Center and Research Institute; and Jenny C. Chang of Houston Methodist Hospital.

This work was supported in part by the National Institutes of Health (grants CA175094, U54MH074404, P30-CA076292), Rendina Family Foundation, Shear Family Foundation, ThinkPink Kids Foundation, the State of Florida and Moffitt Cancer Center & Research Institute.
_________
FOR MORE INFORMATION
Derek Duckett Biosketch
The Duckett Lab
Science Translational Medicine
About the Author
  • The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 2,700 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists-including two Nobel laureates-work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
You May Also Like
JUL 17, 2018
Cell & Molecular Biology
JUL 17, 2018
A New Player in the Control of Cell Division
Oil and water don't mix; cells can take advantage of that phenomenon, phase separation, to organize stuff without using membranes...
AUG 02, 2018
Genetics & Genomics
AUG 02, 2018
The Genetic Hotspots That Can Lead to Cancer
In some of our body's tissues, cells have to replicate many times. That introduces a chance for new genetic errors every time....
AUG 21, 2018
Cancer
AUG 21, 2018
Theranostics.....Heard of it?
Theranostics is an emerging field that combines therapeutics and diagnostic capabilities into one opportunity for treatment of diseases, especially cancer....
SEP 12, 2018
Microbiology
SEP 12, 2018
Researchers ID a Link Between a Bacterial Strain and Gastric Cancer
Helicobacter pylori is a bacterium that causes stomach ulcers, and can lead to gastric cancer....
OCT 21, 2018
Technology
OCT 21, 2018
New Technology Detects Early-Stage Lung Cancer
According to recent research published in the Journal of Molecular Diagnostics, outcomes of patients with non-small-cell lung carcinoma (NSCLC) may be impr...
OCT 29, 2018
Neuroscience
OCT 29, 2018
Gut: a second brain and novel therapeutic target
Undersatnding the role of gut microbiome in disease pathologies and targetting them for potential treatment strategies....
Loading Comments...