COMBINATION THERAPY FOR PIK3CA-ASSOCIATED DISEASES OR DISORDERS
Disclosed herein are methods of treating a cancer comprising administering an inhibitor of at least one kinase in the insulin-receptor/PI3K/AKT/mTOR pathway. In some embodiments, the kinase inhibitor is administered with an insulin suppressing diet.
77 . A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject:
a) an insulin suppressing meal;
b) about 100 to about 900 mg of an inhibitor of at least one kinase in the insulin receptor/PI3K/AKT/mTOR pathway; and
c) a therapeutically effective amount of a taxane-based chemotherapeutic agent, thereby treating the cancer in the subject.
78 . The method of claim 77 , wherein the cancer comprises a PIK3Cα mutation.
79 . The method of claim 77 , wherein the cancer comprises a PTEN loss-of-function mutation.
80 . (canceled)
81 . The method of claim 77 , wherein the cancer is a solid tumor.
82 . The method of claim 77 , wherein the cancer is ovarian cancer.
83 . The method of claim 77 , wherein the cancer is endometrial cancer.
84 . The method of claim 77 , wherein the cancer is endometrial adenocarcinoma.
85 . The method of claim 77 , wherein the cancer is ovarian clear cell carcinoma.
86 . The method of claim 77 , wherein the cancer is ovarian endometrioid carcinoma.
87 . The method of claim 77 , wherein the cancer is colorectal cancer.
88 . The method of claim 77 , wherein the subject is on an insulin suppressing diet that comprises the insulin suppressing meal.
89 . The method of claim 88 , wherein the insulin suppressing diet comprises at least two insulin suppressing meals daily.
90 .- 93 . (canceled)
94 . The method of claim 88 , wherein the insulin suppressing diet comprises a protein content of about 0.8-1.0 g/kg of a reference weight of the subject.
95 . (canceled)
96 . The method of claim 88 , wherein the insulin suppressing diet comprises about 80-90% of total calories from fat.
97 .- 98 . (canceled)
99 . The method of claim 88 , wherein the insulin suppressing diet comprises about 5-15% of total calories from protein.
100 . (canceled)
101 . The method of claim 88 , wherein the insulin suppressing diet comprises about 1-10% of total calories from carbohydrate.
102 .- 103 . (canceled)
104 . The method of any one of claim 88 , wherein the insulin suppressing diet comprises about 20-40 kcal/kg of a reference weight of the subject.
105 . The method of claim 88 , wherein the insulin suppressing diet comprises about 30-35 kcal/kg of a reference weight of the subject having a BMI<30 kg/m 2 or about 25-30 kcal/kg of a reference weight of the subject having a BMI>kg/m 2 .
106 .- 114 . (canceled)
115 . The method of claim 77 , wherein the administering of the inhibitor of the at least one kinase in the insulin receptor/PI3K/AKT/mTOR pathway is three consecutive days per week followed by four consecutive days without administering the inhibitor of the at least one kinase in the insulin receptor/PI3K/AKT/mTOR pathway.
116 .- 122 . (canceled)
123 . The method of claim 77 , wherein the method comprises administering about 100 mg to about 600 mg of the inhibitor of the at least one kinase in the insulin receptor/PI3K/AKT/mTOR pathway.
124 . (canceled)
125 . The method of claim 77 , wherein the inhibitor of the of the at least one kinase in the insulin receptor/PI3K/AKT/mTOR pathway is a PI3K inhibitor.
126 . The method of claim 77 , wherein the inhibitor of the of the at least one kinase in the insulin receptor/PI3K/AKT/mTOR pathway is a PI3Kα inhibitor.
127 . The method of claim 77 , wherein the inhibitor of the at least one kinase in the insulin receptor/PI3K/AKT/mTOR pathway is serabelisib, idelalisib, copanlisib, buparlisib (BKM120), alpelisib (BYL719), taselisib (GDC-0032), pictilisib (GDC-0941), apitolisib (GDC-0980), or dactolisib.
128 .- 135 . (canceled)
136 . The method of claim 77 , wherein the inhibitor of the at least one kinase in the insulin receptor/PI3K/AKT/mTOR pathway is an AKT inhibitor.
137 . The method of claim 77 , wherein the inhibitor of the at least one kinase in the insulin receptor/PI3K/AKT/mTOR pathway is MK-2206.
138 . The method of claim 77 , wherein the inhibitor of the at least one kinase in the insulin receptor/PI3K/AKT/mTOR pathway is an inhibitor of the insulin receptor.
139 . The method of claim 77 , wherein the inhibitor of the at least one kinase in the insulin receptor/PI3K/AKT/mTOR pathway is linsitinib.
140 . (canceled)
141 . The method of claim 77 , wherein the taxane-based chemotherapeutic agent is paclitaxel.
142 .- 143 . (canceled)
144 . The method of claim 77 , wherein the therapeutically effective amount of the taxane-based chemotherapeutic agent is about 80 mg/m 2 .
145 .- 147 . (canceled)
148 . The method of claim 77 , wherein the administering of the taxane-based chemotherapeutic agent is intravenous.
149 .- 396 . (canceled)