Enzyme Demonstrates Effectiveness as a Targeted Therapy in Hard-to-treat Subtypes of Breast Cancer

Findings from a recently published study suggest a potent new therapeutic approach for several hard-to-treat subtypes of breast cancers.

The study, published in Science Translational Medicine (doi:10.1126/scitranslmed.aac8773), points to the enzyme casein kinase 1δ (CK1δ), a critical regulator of growth, as a novel and highly vulnerable therapeutic target. Increased CK1δ expression is common in breast cancer, including the difficult-to-treat subtype triple-negative breast cancer (TNBC), affecting 10% to 20% of patients with breast cancer.

The study is a collaboration between the laboratories of Derek Duckett, PhD, and William R. Roush, PhD, both of The Scripps Research Institute (TSRI), in Jupiter, Florida, and John Cleveland, PhD, formerly of TSRI and currently at the Moffitt Cancer Center in Tampa, Florida.

"Our findings confirm that aberrant CK1δ regulation promotes tumor growth in breast cancers by activating the protein β-catenin," said Duckett. "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."

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

To confirm the new target, the researchers used SR-3029, the Roush lab compound. 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."

"These results are just the tip of the iceberg," added Roush. "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."

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