Biopsies from the same patients before and after treatment reveal how a specific drug reprograms prostate cancer tumors. For more than a decade, drugs like enzalutamide (also known by the brand name Xtandi) that inhibit male hormones from activating the androgen receptor have been used to treat a
In three of the 21 cases Joshi Alumkal and his team studied, the gene expression of the prostate tumors changed after receiving enzalutamide and no longer had the androgen receptor as an engine. Credit: Courtesy of Joshi Alumkal
A new study suggests androgen receptor inhibitors can fundamentally rewire and reshape how prostate tumors function. In fact, in some instances, they can even make tumors more aggressive. These findings from theMale hormones function as fuel, turning on the androgen receptor that acts as the engine of prostate cancer cells. For the past 80 years, treatment for patients with advanced prostate cancer has focused on interfering with these hormone levels.
He and colleagues recruited patients for a longitudinal study to obtain metastatic biopsies before enzalutamide treatmentat the time the tumor became resistant to treatment. Serial biopsies from 21 patients were collected by his team, enabling them to understand the workarounds in the tumor from each patient.
When they compared the baseline sample to the progression sample from the same patient, most tumors showed no significant gene expression changes. “That the gene expression program of a tumor prior to treatment looked very similar at progression while on enzalutamide is quite remarkable,” Alumkal says. “It speaks to how well most of the tumors were able to adapt and keep the androgen receptor engine on despite enzalutamide treatment.
“Our work showed that the majority of the tumors—even after receiving enzalutamide—remain very fuel-dependent, which suggests that continuing to target the androgen receptor could make an enormous difference in these tumors,” Alumkal continued.
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