Abstract
Prostate cancer patients with localized disease are treated with curative intent. However, the disease will recur in approximately 30% of patients with a high incidence of morbidity and mortality. Prognostic biomarkers are needed to identify patients with high risk of relapse. mTOR pathway activation is reported in prostate cancer, but clinical trials testing efficacy of mTOR inhibitors were unsuccessful. To explain this clinical observation, we studied the expression and prognostic impact of mTOR-S2448 phosphorylation in localized prostate carcinomas. mTOR-S2448 phosphorylation is indicative for an activated mTOR pathway in prostate cancer. Surprisingly, the mTOR signaling pathway is activated specifically in prostate cancer patients with a favorable outcome. Since tumors from poor-outcome patients have low levels of mTOR-S2448 phosphorylation, this may explain why mTOR inhibitors proved unsuccessful in prostate cancer trials.
Highlights
IntroductionCurrent diagnostic methods for prostate cancer include serum concentration of prostate specific antigen (PSA) measurement and digital rectal examination (DRE), often followed by transrectal ultrasound-guided biopsies for histological determination [2]
Prostate cancer is the second most common malignancy in men worldwide [1]
Immunohistochemical analysis of the evaluable prostate cancer tissue demonstrated submembranous phosphorylation of mTOR (p-mTOR) staining in 182 cases (95%), negative staining in 9 cases (5%) or at least 1 core negative in 36 cases (19%)
Summary
Current diagnostic methods for prostate cancer include serum concentration of prostate specific antigen (PSA) measurement and digital rectal examination (DRE), often followed by transrectal ultrasound-guided biopsies for histological determination [2]. These tools are used for treatment selection and prognostication. There is a pressing clinical need for prognostic markers to distinguish the patients with a low-risk from those with a high-risk of relapse. Such prognostic factors would prevent overtreatment, and identify those patients who may benefit from additional therapies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
