Docetaxel therapy is approved for castration-resistant metastatic prostate cancer. However, it is unknown whether docetaxel should be added to the treatment regimen after patients become resistant to androgen deprivation therapy or only once they develop metastasis. Therefore, the aim of the study was to identify demographic, clinical and genetic predictors of docetaxel response which would help optimize both its use and timing for initiation.
A total of 209 prostate cancer patients were analyzed for factors predicting GRID (genome resource information database) gene expression scores for docetaxel response (score = 1-100) using linear regression. Factors included in the analysis were age, race, stress, comorbidity measured by TIBI-CaP (Total Illness Burden Index–Carcinoma Prostate), androgen receptor signaling and tumor proliferation signaling gene signatures, PSA (prostate specific antigen) levels, and Gleason grade.
African American men had significantly lower docetaxel sensitivity compared to Whites based on GRID gene signatures. In a regression analysis, however, only comorbidity (β = -0.93, p=0.05), increasing androgen receptor signaling (β = 0.60, p <0.001) and tumor proliferation signaling gene signatures (β = 0.39, p <0.001) were significant predictors of genetics of docetaxel response independent of race. Additionally, TIBI-CaP was significantly correlated with tumor proliferation. The model explained 42% variance in the genetics of docetaxel response.
Optimization of docetaxel therapy use in prostate cancer should take into account patient’s comorbidity, androgen receptor signaling and tumor proliferation signaling gene signatures. Comorbidity may be exerting its effect on docetaxel response by increasing the chances of proliferation of the prostate tumor cells. The pharmacogenomics of docetaxel response could aid precision medicine initiatives by improving survival rates in prostate cancer patients.
The authors.
California Initiative to Advance Precision Medicine.
All authors have declared no conflicts of interest.