Combination therapy using PDK1 and PI3K inhibitors
AssigneeMemorial Sloan Kettering Cancer Center
InventorsPau Castel, Jose Baselga, Maurizio Scaltriti
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Abstract
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.
Claims9
A method of treating a FOXO3-associated cancer in a subject who is resistant to a phosphoinositide 3-kinase (PI3K) inhibitor monotherapy, comprising:
- (a) sensitizing the subject to the PI3K inhibitor, wherein the sensitizing comprises administering to the subject an effective amount of a 3-phosphoinositide dependent protein kinase-1 (PDK1) inhibitor, a serine/threonine-protein kinase (SGK1) inhibitor, or a combination thereof;
- and
- (b) administering to the subject an effective amount of the PI3K inhibitor, wherein the PI3K inhibitor is BYL719 (apelisib), the PDK1 inhibitor is GSK2334470 or a nucleic acid that specifically binds to a nucleic acid encoding PDK1 and reduces PDK1 activity and/or expression, and the SGK1 inhibitor is a nucleic acid that specifically binds to a nucleic acid encoding SGK1 and reduces SGK1 activity and/or expression or a small molecule comprising a pyrazolo(3,4-b)pyrazine head.
Dependencies are inferred from the claim text.