THERAPEUTIC TARGETING OF CASEIN KINASE 1 IN BREAST CANCER

摘要

The invention provides a method of inhibiting casein kinase 1δ (CK1δ), comprising contacting the CK1δ with a compound of formula (I), as defined herein; such as compound SR-3029. We demonstrate that CSNK1D is amplified and/or overexpressed in human breast tumors and that CK1δ can be medically targeted in human breast cancer subtypes overexpressing this kinase. The invention further provides a method of treating cancer, such as a breast cancer, melanoma, glioblastoma, medulloblastoma, renal, bladder or colon cancer, or a cancer that metastasizes to the brain, lung, or bone provided that both elevated CK1δ and β-catenin dependence are involved in those metastatic diseases. The cancer can be a breast cancer of the triple negative subclass of breast cancers (TNBC), or can be an HER+ breast cancer.