Methods for targeting solid tumor stem cells in a solid tumor using a notch4 receptor antagonist

US7850961B2 · kind B2 · utility

Assignee

• THE REGENTS OF THE UNIVERSITY OF MICHIGAN · US

Inventors

• Michael F. Clarke · Ann Arbor, US
• Sean Morrison · Ann Arbor, US
• Max S. Wicha · Ann Arbor, US
• Muhammad Al-Hajj · Cambridge, US

Key dates

• Filing date: Sep 29, 2006
• Grant date: Dec 14, 2010
• Expiry date: Jan 4, 2028

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2503/02
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. We have developed a xenograft model in which we have been able to establish tumors from primary tumors via injection of tumors in the mammary gland of severely immunodeficient mice. These xenograft assay have allowed us to do biological and molecular assays to characterize clonogenic solid tumor stem cells. We have also developed evidence that strongly implicates the Notch pathway, especially Notch 4, as playing a central pathway in carcinogenesis.