Memorial Sloan Kettering Cancer Center

The General Hospital Corporation

Jose Baselga

Maurizio Scaltriti

Pau Castel

Scott A Armstrong

Eneda Toska

Eulalia Baselga

The present invention relates to methods and compositions for inhibiting growth and proliferation of cancer cells resistant to PI3K inhibition using a combination of PDK1, SGK1 and PI3K inhibitors. The present invention is also directed to methods of treating cancer in a subject exhibiting cancer cells resistant to PI3K inhibition, comprising administering inhibitors of PI3K in combination with inhibitors of PDK1 and/or SGK1 to the subject.

Combination therapy using PDK1 and PI3K inhibitors

The presently disclosed subject matter relates to the administration of a KMT2D inhibitor for the treatment of a cancer. The present invention is based on the discovery that upon PI3K inhibition, KMT2D activity is upregulated, resulting in an increase in the expression of genes involved in breast cancer cell proliferation and tumor growth. Accordingly, the present invention provides methods for treating a subject that has cancer by administering a therapeutically effective amount of an KMT2D inhibitor.

Inhibition of KMT2D for the treatment of cancer

The present disclosure relates to methods of treating a vascular malformation in a subject expressing a gain-of-function mutation in a PIK3CA gene comprising administering, to the subject, an effective amount of an agent that inhibits phosphoinositide 3-kinase ('PI3K').

Use of phosphoinositide 3-kinase inhibitors for treatment of vascular malformations

The invention provides combinations comprising GDC-0068 or GDC-0941, or a pharmaceutically acceptable salt thereof and ME-HD7945A. The combinations are particularly useful for treating hyperproliferative disorders, such as cancer (e.g., triple negative breast cancer).

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New York, NY, United States of America

Jose Baselga