Compositions and methods for treating and diagnosing cancer

摘要

The present invention relates to compositions and methods for characterizing, diagnosing and treating cancer. In particular, the present invention identifies LGR5 as a protein over-expressed in solid tumor stem cells. The present invention further identifies an interaction between RSPO1 and LGR5 as an alternative pathway for the activation of beta-catenin signaling. In certain embodiments, the present invention provides biomolecules that disrupt functional signaling via a LGR protein, including, in certain embodiments, molecules that inhibit the interaction between one or more RSPO proteins and one or more LGR proteins, such as LGR5. In certain embodiments, the present invention provides methods of treating cancer comprising disrupting functional LGR signaling and inhibiting growth of a solid tumor comprising solid tumor stem cells.

主权项

1. A method of treating cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of a soluble receptor comprising an extracellular domain of a human leucine-rich repeat-containing G protein-coupled receptor (LGR) protein,
wherein the soluble receptor binds a human R-spondin (RSPO) protein, and wherein the soluble receptor: (a) disrupts RSPO activation of LGR signaling, and/or (b) disrupts RSPO binding to LGR.