ABSTRACT
Reprogramming of metabolism is a hallmark of tumors, which has been explored for therapeutic purposes. Prostate cancer (PCa), particularly advanced and therapy-resistant PCa, displays unique metabolic properties. Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes. Among the many nutrients, glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa. In addition to amino acid metabolism, glutamine is also widely involved in the synthesis of other macromolecules and biomasses. Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients. This review summarizes the metabolic landscape of PCa, with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa, and suggests novel therapeutic strategies.
Subject(s)
Male , Humans , Glutamine/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapyABSTRACT
Prostate cancer is among the most common malignancies in Western countries, and its incidence is rapidly rising in Asia where it was traditionally considered an uncommon tumor. Our understanding of the disease and management strategies continue to evolve. The first revolution of its treatment was in the 1940s when hormonal therapy was used to treat patients. The discovery of prostate-specific antigen (PSA) and the subsequent adoption of widespread PSA screening have made it possible to diagnose the disease early, but it was not until recently that the field realized that we had been overdiagnosing and overtreating a large number of men with indolent diseases that will not impact their quality of life or life expectancy. Distinguishing indolent tumors from aggressive ones remains a challenge, although recent advances in multiparametric MRI have given clinicians more confidence in choosing men for active surveillance. However, more need to be done to fundamentally understand the molecular and cellular bases that determine the biologic behavior of each of the tumors.
Subject(s)
Humans , Male , Androgen Antagonists , Disease Progression , Prostatic Neoplasms/therapyABSTRACT
Objective To investigate the histopathological characteristics of metastatic castration-resistant prostate cancer.Methods Clinical findings,morphologic features,immunophenotypes of androgen receptor (AR),prostatic specific antigen (PSA),chromogranin A (CgA),and phosphatase and tensin homolog deleted on chromosome ten(PTEN)(by EnVision method) of 178 core biopsies from patients with metastatic castration resistant prostate cancer encountered from January 2010 to January 2015 from West Coast Dream Team were analyzed.Results In the 178 cases,51(28.7％)were diagnosed with typical adenocarcinoma,41 cases(23.0％)with intermediate atypical carcinoma and 24 cases(13.5 ％)with small cell carcinoma.The expression of PSA was significantly lower in patients with intermediate atypical carcinoma or with small cell carcinoma(31/39,79.5 ％) than in those with adenocarcinoma(20/20,100 ％).The expression of PTEN was significantly higher in patient with intermediate atypical carcinoma or with small cell carcinoma (31/46,67.4％) than in those with adenocarcinoma (19/41,46.3％).Conclusions Three histopathological subtypes exists in metastatic castration-resistant prostate cancer,including adenocarcinoma,intermediate type atypical carcinoma and small cell carcinoma.They are entities with unique pathological features.The expression of PTEN is significantly lower in the patients with intermediate atypical carcinoma or with small cell carcinoma than in those with adenocarcinoma,indicating that intermediate atypical carcinoma and small cell carcinoma are different from typical adenocarcinoma in tumor occurrence and progression.