Aveo Pharmaceuticals, Inc.

Tesaro, Inc.

Yinghui Zhou

Murray Robinson

Ronan O'Hagan

Steven C Clark

Jie Lin

Tyler E Jacks

Maria Isabel Chiu

Lorena Lerner

Zebin Wang

Joerg Heyer

Keith W Mikule

Ronald A Depinho

William Rideout, Iii

Karuppiah Kannan

Ti Cai

Ronald Depinho

William Iii Rideout

The present disclosure relates to combination therapies containing one or more PARP inhibitors and one or more angiogenesis inhibitor. Also described herein are therapeutic uses of such combination therapies for treating various disorders and conditions. The combination therapies and uses thereof can be useful for preventing tumor cell growth, preventing tumor metastasis, inducing an immune response or enhancing an immune response.

Combination therapies and uses thereof

Chimeric nonhuman mammals useful as inducible spontaneous cancer models are disclosed. The nonhuman mammals are obtained by introducing one or more genetically modified embryonic stem (ES) cells into an early stage embryo, and then implanting the manipulated embryo into a surrogate mother. The ES cells contain a recombinant oncogene, and also may contain a genetic mutation that deletes or inactivates a tumor suppressor gene. Models of different types of cancer are produced by introducing different combinations of genetic mutations into the ES cells that are introduced into the early stage embryo.

Chimeric cancer models

A method of producing a tumorigenic mouse cell, the tumorigenicity of which depends on a recombinant gene of interest is disclosed. The method involves: (a) providing a conditionally tumorigenic mouse cell containing a recombinant oncogene operably linked to an inducible promoter, wherein (i) expression of the recombinant oncogene is necessary and sufficient for the tumorigenicity of the tumorigenic mouse cell, and (ii) the inducible promoter is in the uninduced state; and (b) introducing into the cell a recombinant gene of interest that functionally complements the oncogene, thereby restoring tumorigenicity without expression of the inducible recombinant oncogene. Also disclosed is a method of testing a compound for anti-tumor effects. The method includes producing tumorigenic mouse cells the tumorigenicity depends on expression of a recombinant gene of interest, implanting the cells in mice and obtaining tumors from the implanted cells, administering test compounds to the mice, and determining anti-tumor effects, if any, of the compounds.

Directed complementation

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Belmont, MA, United States of America

Yinghui Zhou