Method of treating androgen receptor (AR)-positive breast cancers with selective androgen receptor modulator (SARMs)

摘要

This invention relates to the treatment of androgen receptor-positive breast cancer in a subject, for example a female subject. Accordingly, this invention provides methods of: a) treating a subject suffering from breast cancer; b) treating a subject suffering from metastatic breast cancer; c) treating a subject suffering from refractory breast cancer; d) treating a subject suffering from AR-positive breast cancer; e) treating a subject suffering from AR-positive refractory breast cancer; f) treating a subject suffering from AR-positive metastatic breast cancer; g) treating a subject suffering from AR-positive and ER-positive breast cancer; h) treating a subject suffering from triple negative breast cancer; i) treating a subject suffering from advanced breast cancer; j) treating a subject suffering from breast cancer that has failed SERM (tamoxifen, toremifene), aromatase inhibitor, trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, exemestane (Aromasin), bevacizumab (Avastin), and/or fulvestrant treatments; k) treating, preventing, suppressing or inhibiting metastasis in a subject suffering from breast cancer; l) prolonging survival of a subject with breast cancer, and/or m) prolonging the progression-free survival of a subject with breast cancer; comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound, comprising administering to the subject a therapeutically effective amount of a SARM compound of this invention.

主权项

1. A method of treating, inhibiting, or reducing the severity of triple-negative breast cancer in a subject with triple-negative breast cancer, comprising administering to said subject a selective androgen receptor modulator (SARM) compound represented by a structure of formula I: wherein
X is O;G is O;T is OH;R is alkyl, dihaloalkyl, trihaloalkyl, CH2F, CHF2, CF3, CF2CF3, aryl, alkenyl or OH;R1 is CH3, CH2F, CHF2, CF3, CH2CH3, or CF2CF3;R2 is H, F, Cl, Br, I, CH3, CF3, OH, CN, NO2, NHCOCH3, NHCOCF3, NHCOR, alkyl, arylalkyl, OR, NH2, NHR, N(R)2 or SR;R3 is H, F, Cl, Br, I, CN, NO2, COR, COOH, CONHR, CF3, or Sn(R)3;Z is NO2, CN, COR, COOH, or CONHR;Y is CF3, F, Br, Cl, I, CN, or Sn(R)3;Q is CN, alkyl, halogen, N(R)2, NHCOCH3, NHCOCF3, NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH3, NHCSCF3, NHCSR, NHSO2CH3, NHSO2R, OR, COR, OCOR, OSO2R, SO2R or SR;n is an integer of 1-4;m is an integer of 1-3; and wherein said treating does not include preventing.