US 11,696,924 B2
Combination therapy using PDK1 and PI3K inhibitors
Pau Castel, New York, NY (US); Jose Baselga, New York, NY (US); and Maurizio Scaltriti, New Yok, NY (US)
Assigned to MEMORIAL SLOAN-KETTERING CANCER CENTER, New York, NY (US)
Filed by MEMORIAL SLOAN-KETTERING CANCER CENTER, New York, NY (US)
Filed on Jan. 17, 2018, as Appl. No. 15/873,324.
Application 15/873,324 is a continuation of application No. PCT/US2016/042616, filed on Jul. 15, 2016.
Claims priority of provisional application 62/194,106, filed on Jul. 17, 2015.
Prior Publication US 2018/0147232 A1, May 31, 2018
Int. Cl. A61K 31/713 (2006.01); A61K 31/506 (2006.01); A61K 31/4439 (2006.01); A61K 31/7105 (2006.01); A61K 31/711 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01)
CPC A61K 31/713 (2013.01) [A61K 31/4439 (2013.01); A61K 31/506 (2013.01); A61K 31/711 (2013.01); A61K 31/7105 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01)] 9 Claims
OG exemplary drawing
 
1. 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.