METHODS FOR TREATING CANCER
Disclosed herein are methods of inhibiting tumor growth or producing tumor regression in a subject by administering to the subject a therapeutically effective amount of a combination of palbociclib and RAD1901.
1 - 18 . (canceled)
19 . A method of treating breast cancer in a subject having an estrogen receptor alpha-positive cancer that is drug-resistant and has a mutant estrogen receptor alpha comprising administering to said subject a therapeutically effective amount of a combination of a cdk4/6 inhibitor and RAD1901 having the structure:
or a salt or solvate thereof.
20 . The method of claim 19 wherein said drug resistant breast cancer is resistant to one or more antiestrogen or aromatase inhibitor therapies.
21 . The method of claim 20 wherein said one or more antiestrogens are selected from the group consisting of tamoxifen, toremifene and fulvestrant and said one or more aromatase inhibitors are selected from the group consisting of aromasin, letrozole and anastrozole.
22 . The method according to claim 19 wherein said subject expresses at least one mutant estrogen receptor alpha selected from the group consisting of D538G, Y537S, Y537N, Y537C, E380Q, S463P, L536R, L536Q, P535H, V392I and V534E.
23 . The method of claim 22 wherein said mutant estrogen receptor alpha is selected from the group consisting of Y537S, Y537N, Y537C, D538G, L536R, S463P and E380Q
24 . The method according to claim 22 wherein said mutant receptor alpha is Y537S.
25 . (canceled)
26 . The method according to claim 19 wherein said RAD1901 is administered in a total daily dosage of from between 100 mg and 1,000 mg.
27 . The method according to claim 26 wherein said RAD1901 is administered in a total daily dosage of 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg or 1,000 mg.
28 . The method according to claim 25 wherein said daily dosage is delivered in two separate doses.
29 . The method according to claim 28 wherein said separate doses are equal doses.
30 - 31 . (canceled)
32 . The method according to claim 19 wherein said woman is post-menopausal.
33 . The method according to claim 19 wherein said woman is first identified for treatment through measuring for increased expression of one or more genes selected from ABL1, AKT1, AKT2, ALK, APC, AR, ARID1A, ASXL1, ATM, AURKA, BAP, BAP1, BCL2L11, BCR, BRAF, BRCA1, BRCA2, CCND1, CCND2, CCND3, CCNE1, CDH1, CDK4, CDK6, CDK8, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CEBPA, CTNNB1, DDR2, DNMT3A, E2F3, EGFR, EML4, EPHB2, ERBB2, ERBB3, ESR1, EWSR1, FBXW7, FGF4, FGFR1, FGFR2, FGFR3, FLT3, FRS2, HIF1A, HRAS, IDH1, IDH2, IGF1R, JAK2, KDM6A, KDR, KIF5B, KIT, KRAS, LRP1B, MAP2K1, MAP2K4, MCL1, MDM2, MDM4, MET, MGMT, MLL, MPL, MSH6, MTOR, MYC, NF1, NF2, NKX2-1, NOTCH1, NPM, NRAS, PDGFRA, PIK3CA, PIK3R1, PML, PTEN, PTPRD, RARA, RB1, RET, RICTOR, ROS1, RPTOR, RUNX1, SMAD4, SMARCA4, SOX2, STK11, TET2, TP53, TSC1, TSC2, and VHL.
34 . The method according to claim 33 wherein said one or more genes is selected from AKT1, AKT2, BRAF, CDK4, CDK6, PIK3CA, PIK3R1 and MTOR.
35 . The method according to claim 19 wherein said cdk4/cdk6 inhibitor is selected from the group consisting of abemaciclib, ribociclib and palbociclib.
36 . The method according to claim 35 wherein said cdk4/6 inhibitor is palbociclib.
37 . The method according to claim 36 wherein said palbociclib is dosed at a daily dose of from between 25 mg and 250 mg.
38 - 41 . (canceled)
42 . The method according to claim 36 wherein said palbociclib is dosed for 21 days in a 28 day cycle.
43 - 60 . (canceled)
61 . The method according to claim 34 wherein said cdk4/6 inhibitor is abemaciclib.
62 . The method according to claim 61 wherein said abemaciclib is dosed at a daily dose of 300 mg.
63 . (canceled)
64 . The method according to claim 61 wherein said abemaciclib is dosed for 28 days in a 28 day cycle.
65 - 70 . (canceled)