Abstract: Isolated antibodies that specifically binds to an extracellular conserved ligand binding region of a human Notch receptor and inhibits growth of a tumor are described. Also described are methods of treating cancer, the method comprising administering an anti-Notch antibody in an amount effective to inhibit tumor growth.

Abstract: The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides a soluble FZD receptor comprising an extracellular domain of a human FZD receptor that inhibits growth of tumor cells. The present invention still further provides a soluble receptor comprising a Fri domain of a human FZD receptor that binds a ligand of a human FZD receptor and said soluble receptor is capable of inhibiting tumor growth. The present invention still further provides a method of treating cancer comprising administering a soluble FZD receptor comprising for example, either an extracellular domain of a human FZD receptor or a Fri domain of a human FZD receptor, in an amount effective to inhibit tumor growth.

Abstract: 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.

Abstract: Methods for treating cancer comprising administering a DLL4 antagonist and one or more anti-hypertensive agents are described. Also described are pharmaceutical compositions comprising a DLL4 antagonist and one or more anti-hypertensive agents, and kits comprising the same.

Abstract: The present invention relates to VEGF-binding agents, DLL4-binding agents, VEGF/DLL4 bispecific binding agents, and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human VEGF, antibodies that specifically bind human DLL4, and bispecific antibodies that specifically bind human VEGF and/or human DLL4. The present invention further provides methods of using the agents to inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

Abstract: The present invention relates to Notch1 binding agents and methods of using the agents for treating diseases, such as hematologic cancers. The present invention provides antibodies that specifically bind to a non-ligand binding membrane proximal region of the extracellular domain of human Notch1. The present invention further provides methods of using agents that inhibit Notch1 activity for treating cancer. Also described are methods of treating hematologic cancers comprising administering a therapeutically effective amount of a binding agent or antibody of the present invention to a subject having a hematologic cancer such as T-cell lymphoblastic leukemia.

Abstract: Methods for treating diseases such as cancer comprising administering a Wnt pathway inhibitor, either alone or in combination with other anti-cancer agents, and monitoring for skeletal-related side effects and/or toxicity.

Abstract: Methods for treating diseases such as cancer comprising administering a DLL4 antagonist, either alone or in combination with other anti-cancer agents, and monitoring for cardiovascular side effects and/or toxicity.

Abstract: Monoclonal antibodies that specifically bind to an extracellular domain of human Jagged 1 and inhibit growth of a tumor comprising cancer stem cells are described. Also described is a method of treating cancer that comprises administering a therapeutically effective amount of a monoclonal anti-Jagged 1 antibody.

Abstract: The present invention relates to RSPO-binding agents and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human RSPO proteins and modulate ?-catenin activity. The present invention further provides methods of using agents that modulate the activity of RSPO proteins, such as antibodies that specifically bind RSPO1, RSPO2, and/or RSPO3 and inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

Abstract: Methods for treating diseases such as cancer comprising administering a DLL4 antagonist, either alone or in combination with other anti-cancer agents, and monitoring for cardiovascular side effects and/or toxicity.

Abstract: The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides an antibody that specifically binds to a non-ligand binding region of the extracellular domain of a human NOTCH receptor and inhibits growth of tumor cells. The present invention further provides a method of treating cancer, the method comprising administering a therapeutically effective amount of an antibody that specifically binds to a non-ligand binding region of the extracellular domain of a human NOTCH receptor protein and inhibits growth of tumor cells.

Abstract: The present invention relates to DDR1 binding agents and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind to an extracellular domain of DDR1 and modulate DDR1 activity. The present invention further provides methods of using agents that modulate the activity of DDR1, such as antibodies that specifically bind DDR1, to reduce the tumorigenicity of tumors comprising cancer stem cells by reducing the frequency or number of cancer stem cells in the tumor. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

Abstract: An isolated antibody that specifically binds to an extracellular domain of human DDR2 and has a therapeutic effect on a solid tumor is described. Also described is a method of treating cancer, the method comprising administering to a patient having a solid tumor an antibody of the present disclosure in a therapeutically effective amount.

Abstract: Binding agents that modulate the immune response are disclosed. The binding agents may include soluble receptors, polypeptides, and/or antibodies. Also disclosed are methods of using the binding agents for the treatment of diseases such as cancer.

Abstract: The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides a soluble FZD receptor comprising an extracellular domain of a human FZD receptor that inhibits growth of tumor cells. The present invention still further provides a soluble receptor comprising a Fri domain of a human FZD receptor that binds a ligand of a human FZD receptor and said soluble receptor is capable of inhibiting tumor growth. The present invention still further provides a method of treating cancer comprising administering a soluble FZD receptor comprising for example, either an extracellular domain of a human FZD receptor or a Fri domain of a human FZD receptor, in an amount effective to inhibit tumor growth.

Abstract: 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 cell. 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.

Abstract: Novel methods of treating neuroendocrine tumors are provided. In one embodiment, the method comprises administering to a subject in need thereof a therapeutically effective dose of a Wnt antagonist. In one embodiment, the Wnt antagonist is an anti-FZD antibody. In another embodiment, the Wnt antagonist is a soluble FZD receptor polypeptide. In a further embodiment, the Wnt antagonist is an anti-Wnt antibody.

Abstract: Methods of inhibiting melanoma tumor growth, methods of treating melanoma and metastatic melanoma, and methods of reducing the frequency of tumor initiating cells (or cancer stem cells) in melanoma tumors are described. The methods described comprise administering a DLL4 antagonist (e.g., an antibody that specifically binds the extracellular domain of human DLL4) to a subject. Related polypeptides and polynucleotides, compositions comprising the DLL4 antagonists, and methods of making the DLL4 antagonists are also described.

Abstract: Disclosed are DDR1 binding agents and methods of using the agents for treating diseases such as cancer. The disclosure provides antibodies that specifically bind to an extracellular domain of DDR1 and modulate DDR1 activity. The disclosure further provides methods of using agents that modulate the activity of DDRI, such as antibodies that specifically bind DDR1, to reduce the tumorigenicity of tumors comprising cancer stem cells by reducing the frequency or number of cancer stem cells in the tumor. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.