AR+ breast cancer treatment methods
A method for treating AR+ breast cancer in a subject comprising administering to the subject an AR agonist (e.g., SARMs such as RAD140), or in combination with one or more therapeutic agents selected from the group consisting of cdk4/6 inhibitors, m-TOR inhibitors, PI3k inhibitors, PARP inhibitors, BCL-2 inhibitors, and MCL-1 inhibitors.
1. A method of treating AR+/ER+breast cancer in a subject in need thereof, the method comprising administering to the subject a compound which is RAD140 (Compound III)
a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.
2. The method according to claim 1 , wherein the compound is administered via an oral route.
3. The method according to claim 1 , wherein the subject has had disease progression after treatment with one or more agents selected from the group consisting of CDK4/6 inhibitors, mTOR inhibitors, BCL-2 inhibitors, PI3K inhibitors, and combinations thereof.
4. The method according to claim 1 , wherein the compound is administered to the subject at a dose between 10 and 500 mg.
5. The method according to claim 1 , wherein the subject expresses ERα gene (ESR1) comprising one or more mutations.
6. The method according to claim 5 , wherein said mutation results in a fusion protein containing at least 10 continuous amino acids from a sequence of a non-mutated ESR1 and at least 10 continuous amino acids from another human protein.
7. The method according to claim 5 , wherein said mutation results in ESR1 missing 10 or more consecutive amino acids from its normal (non-mutated) ligand binding domain amino acid sequence.
8. The method according to claim 5 , wherein said mutation comprises one or more mutations selected from the group consisting of ESR1-AKAP12, ESR1-CCDC170, ESR1-YAP1, ESR1-POLH, ESR1-PCDH11X, and combinations thereof.
9. The method according to claim 1 , wherein the treatment further comprises the administration of a CDK4/6 inhibitor.
10. The method according to claim 9 , wherein said CDK4/6 inhibitor has an IC 50 of <100 nM against CDK4 and CDK6.
11. The method according to claim 9 , wherein said CDK4/6 inhibitor is selected from the group consisting of palbociclib, ribociclib, trilaciclib AMG925, and abemaciclib.
12. The method according to claim 11 , wherein said CDK4/6 inhibitor is palbociclib.
13. The method according to claim 1 , wherein said breast cancer is localized, advanced, or metastatic.