Method of treating cancer using selective estrogen receptor modulators

Abstract

Disclosed herein are methods of treating subjects suffering from estrogen receptor positive cancer of the brain by administering a selective estrogen receptor degrader (SERM). Also disclosed are methods of treating a cancer that is resistant to an estrogen receptor modulator by administering a SERM.

1 - 23 . (canceled) 
     
     
         24 . A method of treating breast cancer brain metastasis in a subject, the method comprising administering a compound of (R)-6-{2-{ethyl[4-(2-ethylaminoethyl)benzyl]amino}-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-ol, wherein the breast cancer brain metastasis is resistant to an estrogen receptor modulator and is estrogen receptor positive. 
     
     
         25 . The method of  claim 24 , wherein an effective amount of the compound is administered. 
     
     
         26 . The method of  claim 25 , wherein the effective amount comprises a high dosage. 
     
     
         27 . The method of  claim 26 , wherein the high dosage is more than about 20 mg/kg. 
     
     
         28 . The method of  claim 26 , wherein the high dosage is about 20 mg/kg to about 100 mg/kg. 
     
     
         29 . The method of  claim 24 , wherein the compound is administered by oral administration, intravenous administration, intradermal injection, intramuscular injection, or subcutaneous injection. 
     
     
         30 . The method of  claim 24 , further comprising administering an effective amount of at least one compound selected from the group consisting of a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6 inhibitor), an antiestrogen, a ligand of retinoic acid or retinoxic X receptor, an antiprogestin, an antiandrogen, vitamin D or metabolite thereof, a farnesyl transferase inhibitor, a PPARα or gamma agonist and a MAP kinase inhibitor. 
     
     
         31 . The method of  claim 24 , wherein the breast cancer brain metastasis is de novo resistant to the estrogen receptor modulator. 
     
     
         32 . The method of  claim 24 , wherein the resistance to the estrogen receptor modulator is acquired. 
     
     
         33 . The method of  claim 24 , wherein the estrogen receptor modulator is a selective estrogen receptor modulator (SERM). 
     
     
         34 . The method of  claim 33 , wherein the SERM is tamoxifen, idoxifene, raloxifene, or ICI 182,780. 
     
     
         35 . The method of  claim 24 , wherein the estrogen receptor modulator is an aromatase inhibitor. 
     
     
         36 . The method of  claim 35 , wherein the aromatase inhibitor is anastrozole, letrozole, or exemestane. 
     
     
         37 . A method of treating breast cancer brain metastasis in a subject, the method comprising administering a composition comprising (R)-6-{2-{ethyl[4-(2-ethylaminoethyl)benzyl]amino}-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-ol, wherein the breast cancer brain metastasis is resistant to an estrogen receptor modulator. 
     
     
         38 . The method of  claim 37 , wherein the breast cancer brain metastasis is estrogen receptor positive. 
     
     
         39 . The method of  claim 37 , wherein an effective amount of the composition is administered. 
     
     
         40 . The method of  claim 39 , wherein the effective amount comprises a high dosage. 
     
     
         41 . The method of  claim 40 , wherein the high dosage is more than about 20 mg/kg. 
     
     
         42 . The method of  claim 40 , wherein the high dosage is about 20 mg/kg to about 100 mg/kg. 
     
     
         43 . The method of  claim 37 , wherein the composition is administered by oral administration, intravenous administration, intradermal injection, intramuscular injection, or subcutaneous injection. 
     
     
         44 . The method of  claim 37 , further comprising administering an effective amount of at least one compound selected from the group consisting of a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6 inhibitor), an antiestrogen, a ligand of retinoic acid or retinoxic X receptor, an antiprogestin, an antiandrogen, vitamin D or metabolite thereof, a farnesyl transferase inhibitor, a PPARα or gamma agonist and a MAP kinase inhibitor. 
     
     
         45 . The method of  claim 37 , wherein the breast cancer brain metastasis is de novo resistant to the estrogen receptor modulator. 
     
     
         46 . The method of  claim 37 , wherein the resistance to the estrogen receptor modulator is acquired. 
     
     
         47 . The method of  claim 37 , wherein the estrogen receptor modulator is a selective estrogen receptor modulator (SERM). 
     
     
         48 . The method of  claim 47 , wherein the SERM is tamoxifen, idoxifene, raloxifene or ICI 182,780. 
     
     
         49 . The method of  claim 37 , wherein the estrogen receptor modulator is an aromatase inhibitor. 
     
     
         50 . The method of  claim 49 , wherein the aromatase inhibitor is anastrozole, letrozole, or exemestane.