Impact of therapy on cancer metabolism in high-risk localized prostate cancer treated with neoadjuvant docetaxel and androgen deprivation therapy

Background The application of neoadjuvant docetaxel and androgen deprivation therapy before radical prostatectomy has been clinically recognized as beneficial for the overall and progression-free survival of patients with advanced prostate cancer. However, the mechanism underlying its clinical efficacy has not yet been reported. Methods We conducted a randomized comparative study on about 100 patients with high-risk localized prostate cancer. Through nontarget metabolomics and tissue microarray immunohistochemistry, we investigated the difference in the endogenous metabolism of tumors in patients with prostate cancer who received or did not receive the neoadjuvant therapy. Results Many endogenous metabolic pathways, especially nucleotide synthesis, glutathione metabolism, citric acid cycle, and lipid synthesis, in prostate cancer tissue were altered after the neoadjuvant treatment, and the levels of nearly 90% of the differentially regulated metabolites were significantly decreased. Moreover, the levels of key enzymes in the cellular energy pathways were downregulated in tumor tissues and upregulated in adjacent tissues after the treatment. The positive and negative effects of the neoadjuvant therapy on normal and tumor cells in the prostate, respectively, resulted in the activation of the former and inhibition of the latter, which helped in reducing the number of tumors and weakened their aggressiveness. Conclusions From the perspective of endogenous metabolism in tumors, we have confirmed that neoadjuvant therapy can significantly downregulate important pathways for biosynthesis and energy metabolism in prostate cancer tissue, and thereby, inhibit tumor growth and metastasis.