US2017315127A1PendingUtilityA1

Treatment of metastatic prostate cancer

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Assignee: UNIV CALIFORNIAPriority: Oct 28, 2013Filed: Apr 20, 2016Published: Nov 2, 2017
Est. expiryOct 28, 2033(~7.3 yrs left)· nominal 20-yr term from priority
Inventors:Allen C. GaoChengfei LiuWei LouChong-Xian Pan
A61P 43/00A61P 35/04A61P 35/00A61P 13/08A61K 31/277A61K 31/4166A61K 31/405A61K 31/609A61K 31/58A61K 45/06A61K 31/337A61K 38/00A61P 15/00G01N 33/57555A61K 47/6869C12Q 1/6886C12Q 2600/178G01N 2800/52G01N 33/57434
36
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Claims

Abstract

The present invention provides new compositions and methods for treating prostate cancer, e.g., drug-resistant prostate cancer, such as anti-androgen drug (e.g., enzalutamide) resistant and/or castration resistant prostate cancer (CRPC). These new compositions include, but are not limited to, pharmaceutical compositions that include an AR-V7 inhibitor, such as niclosamide. Alternatively, these new compositions can include, but are not limited to, pharmaceutical compositions that include an AKR1C3 inhibitor, such as indomethacin. These new methods include, but are not limited to, methods of administering an AR-V7 inhibitor, such as niclosamide, and/or an AKR1C3 inhibitor, such as indomethacin, to treat patients having prostate cancer. The present invention also provides methods of inhibiting androgen receptor variant expression, e.g. AR-V7, and methods of killing cells expressing AR-V7. The present invention further provides methods of inhibiting AKR1C3 expression or activity, and methods of killing cells that express AKR1C3.

Claims

exact text as granted — not AI-modified
1 . A composition comprising an AR-V7 inhibitor and a compound selected from the group consisting of enzalutamide, abiraterone, bicalutamide, docetaxel, and combinations thereof. 
     
     
         2 . The composition of  claim 1 , wherein the AR-V7 inhibitor is present in an amount effective to enhance the therapeutic benefit of the compound. 
     
     
         3 . The composition of  claim 1 , wherein the composition further comprises an AKR1C3 inhibitor. 
     
     
         4 . A composition comprising an AKR1C3 inhibitor and a compound selected from the group consisting of enzalutamide, abiraterone, bicalutamide, docetaxel, and combinations thereof. 
     
     
         5 . The composition of  claim 4 , wherein the AKR1C3 inhibitor is present in an amount effective to enhance the therapeutic benefit of the compound. 
     
     
         6 . The composition of  claim 4 , wherein the composition further comprises an AR-V7 inhibitor. 
     
     
         7 - 9 . (canceled) 
     
     
         10 . The composition of  claim 1 , wherein the AR-V7 inhibitor is niclosamide. 
     
     
         11 . The composition of  claim 4 , wherein the AKR1C3 inhibitor is indomethacin. 
     
     
         12 - 37 . (canceled) 
     
     
         38 . A method of enhancing the therapeutic effects of a prostate cancer drug in a patient having prostate cancer, the method comprising administering to a patient in need of prostate cancer treatment an effective amount of an AR-V7 inhibitor and/or an effective amount of an AKR1C3 inhibitor. 
     
     
         39 . The method of  claim 38 , wherein the method comprises administering to the patient an effective amount of the AR-V7 inhibitor. 
     
     
         40 . The method of  claim 38 , wherein the method comprises administering to the patient an effective amount of the AKR1C3 inhibitor. 
     
     
         41 . The method of  claim 38 , wherein the method comprises administering to the patient an effective amount of the AR-V7 inhibitor and an effective amount of the AKR1C3 inhibitor. 
     
     
         42 . The method of  claim 38 , wherein the prostate cancer drug that is enhanced is an anti-androgen drug, docetaxel, or combinations thereof. 
     
     
         43 . The method of  claim 42 , wherein the anti-androgen drug is selected from the group consisting of enzalutamide, abiraterone, bicalutamide, and combinations thereof. 
     
     
         44 . The method of  claim 38 , wherein the AR-V7 inhibitor is niclosamide. 
     
     
         45 . The method of  claim 38 , wherein the AKR1C3 inhibitor is indomethacin. 
     
     
         46 . The method of  claim 38 , wherein the method enhances the therapeutic effects of the prostate cancer drug by resensitizing prostate cancer cells to the prostate cancer drug. 
     
     
         47 . The method of  claim 38 , wherein the prostate cancer is selected from the group consisting of castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, advanced stage prostate cancer, drug-resistant prostate cancer, anti-androgen-resistant prostate cancer, enzalutamide-resistant prostate cancer, abiraterone-resistant prostate cancer, bicalutamide-resistant prostate cancer, docetaxel-resistant prostate cancer, AR-V7-induced drug-resistant prostate cancer, AKR1C3-induced drug-resistant prostate cancer, and combinations thereof. 
     
     
         48 . The method of  claim 38 , wherein the method comprises:
 oral administration of an effective amount of the AR-V7 inhibitor; and/or   oral administration of an effective amount of the AKR1C3 inhibitor.   
     
     
         49 . The method of  claim 38 , wherein the AR-V7 inhibitor and/or the AKR1C3 inhibitor is co-administered with the prostate cancer drug. 
     
     
         50 - 55 . (canceled) 
     
     
         56 . A kit comprising: (a) an AR-V7 inhibitor and/or an AKR1C3 inhibitor; and (b) a compound selected from the group consisting of enzalutamide, abiraterone, bicalutamide, docetaxel, and combinations thereof. 
     
     
         57 . The kit of  claim 56 , further comprising a label with instructions for administering the AR-V7 inhibitor. 
     
     
         58 . The kit of  claim 56 , further comprising a label with instructions for administering the AKR1C3 inhibitor. 
     
     
         59 . The kit of  claim 56 , wherein the AR-V7 inhibitor is niclosamide. 
     
     
         60 . The kit of  claim 56 , wherein the AKR1C3 inhibitor is indomethacin. 
     
     
         61 . The method of  claim 44 , wherein a daily dose of about 500 mg or more niclosamide is administered to the patient per day. 
     
     
         62 . The method of  claim 61 , wherein the daily dose of niclosamide is administered once per day. 
     
     
         63 . The method of  claim 61 , wherein the daily dose of niclosamide is divided into subdoses and administered in multiple doses. 
     
     
         64 . The method of  claim 63 , wherein the multiple doses of niclosamide are administered twice, three times, or four times per day. 
     
     
         65 . The method of  claim 61 , wherein the daily dose of niclosamide is orally administered. 
     
     
         66 . The method of  claim 44 , wherein a daily dose of about 5,000 mg niclosamide is administered to the patient per day. 
     
     
         67 . The method of  claim 66 , wherein the daily dose of niclosamide is divided into subdoses and administered three times per day. 
     
     
         68 . The method of  claim 66 , wherein the daily dose of niclosamide is orally administered.

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