The Notch pathway is involved in normal mammary development, in communication between cells, and in determining what happens to a cell when it divides, thus “regulating the self-renewal of cancer stem cells,” Chang said in an interview with MedPage Today.
She and her team implanted mice with human breast cancer biopsy material that included breast cancer stem cells, then gave them a Notch inhibitor (MRK-003) or a placebo.
MRK-003 significantly reduced formation of clusters of tumor cells called mammospheres compared with placebo.
Given the proposed mechanism, Notch inhibitors are likely to be developed for upfront use in combination with agents to “debulk” the daughter cells or for chronic administration in the adjuvant setting to prevent recurrence, she speculated.
Her group plans a larger Phase II trial, while others are developing agents targeting other cancer stem cell pathways, such as Hedgehog.
