Methods for treating cancer

Abstract

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)