Methods and materials for assessing prostate cancer therapies and compounds
AssigneeThe Regents of the University of California
InventorsMichael Jung, Samedy Ouk, Charles Sawyers, Charlie Chen, Derek Welsbie
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Abstract
A modest (2-5 fold) increase in androgen receptor (AR) mRNA is the only expression change consistently associated with developing resistance to antiandrogen therapy. Increased levels of AR confer resistance to anti-androgens by amplifying signal output from low levels of residual ligand and altering the normal response to antagonists. This invention provides cell based assays for use in the examination of new therapeutic modalities and provides for the design of novel antiandrogen compounds.
Claims14
A composition of matter comprising a compound having the formula
- wherein R is (CH2)nN3 or N3C6H4 and where n is from 3 to 8.
A composition of matter comprising a compound that inhibits the growth of hormone refractory prostate cancer cells, wherein said compound has been previously subjected to a method of examining the physiological effect of said compound on a mammalian prostate cancer cell wherein said prostate cancer cell expresses an exogenous wild type androgen receptor polynucleotide that encodes an androgen receptor polypeptide or an androgen receptor polypeptide variant, said cell further comprising an abnormal level of mRNA that encodes said androgen receptor polypeptide or said androgen receptor polypeptide variant when compared to the level of mRNA that encodes said androgen receptor polypeptide or said androgen receptor polypeptide variant in a normal prostate cell, said method comprising:
- (a) determining that said abnormal level of mRNA in said prostate cancer cell is at least two fold higher than the level of mRNA in said normal prostate cell;
- (b) contacting said compound with said prostate cancer cell to provide a treated prostate cancer cell;
- and
- (c) examining one or more physiological characteristics of said treated prostate cancer cell.
A composition of matter comprising a compound that inhibits the growth of hormone refractory prostate cancer cells, wherein said compound has been previously subjected to a method of examining the physiological effect of said compound on a mammalian prostate cancer cell wherein said prostate cancer cell expresses an exogenous wild type androgen receptor polynucleotide that encodes an abnormal level of androgen receptor polypeptide or an abnormal level of androgen receptor polypeptide variant when compared to the level of androgen receptor polypeptide or androgen receptor polypeptide variant encoded by a normal prostate cell, said method comprising:
- (a) determining that said abnormal level of androgen receptor polypeptide or said abnormal level of androgen receptor polypeptide variant is at least two fold higher than the level of androgen receptor polypeptide or androgen receptor polypeptide variant in said normal prostate cell;
- (b) contacting said compound with said prostate cancer cell to provide a treated prostate cancer cell;
- and
- (c) examining one or more physiological characteristics of said treated prostate cancer cell.
A method for making a composition of matter comprising a compound that inhibits the growth of hormone refractory prostate cancer cells, wherein said method comprises the initial step of examining the physiological effect of said compound on a mammalian prostate cancer cell wherein said prostate cancer cell expresses an exogenous wild type androgen receptor polynucleotide that encodes an androgen receptor polypeptide or an androgen receptor polypeptide variant, said cell further comprising an abnormal level of mRNA that encodes said androgen receptor polypeptide or said androgen receptor polypeptide variant when compared to the level of mRNA that encodes said androgen receptor polypeptide or said androgen receptor polypeptide variant in a normal prostate cell, said initial step comprising:
- (a) determining that said abnormal level of mRNA in said prostate cancer cell is at least two fold higher than the level of mRNA in said normal prostate cell;
- (b) contacting said compound with said prostate cancer cell to provide a treated prostate cancer cell;
- and
- (c) examining one or more physiological characteristics of said treated prostate cancer cell.
A method for making a composition of matter comprising a compound that inhibits the growth of hormone refractory prostate cancer cells, wherein said method comprises the initial step of examining the physiological effect of said compound on a mammalian prostate cancer cell wherein said prostate cancer cell expresses an exogenous wild type androgen receptor polynucleotide that encodes an abnormal level of androgen receptor polypeptide or an abnormal level of androgen receptor polypeptide variant when compared to the level of androgen receptor polypeptide or androgen receptor polypeptide variant encoded by a normal prostate cell, said initial step comprising:
- (a) determining that said abnormal level of androgen receptor polypeptide or said abnormal level of androgen receptor polypeptide variant is at least two fold higher than the level of androgen receptor polypeptide or androgen receptor polypeptide variant in said normal prostate cell;
- (b) contacting said compound with said prostate cancer cell to provide a treated prostate cancer cell;
- and
- (c) examining one or more physiological characteristics of said treated prostate cancer cell.
Dependencies are inferred from the claim text.