Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Abstract

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.

Development of Olaparib-Resistance Prostate Cancer Cell Lines to Identify Mechanisms Associated with Acquired Resistance

“…It is now considered a multi-drug resistance (MDR) mechanism in various cancers, including in PC [ 34 , 35 ]. Some studies suggest that autophagy protects PC cells against hormonotherapy and chemotherapy [ 36 , 37 , 38 , 39 ]. The impact of autophagy in PARPi resistance has been shown primarily in breast cancer but not in PC [ 40 , 41 ].…”

Metabolic syndrome and metastatic prostate cancer correlation study, a real-world study in a prostate cancer clinical research center, Xinjiang, China

“…There are complex and precise hormonal mechanisms of action and clinical metabolic alterations in MetS, and as the prostate is a specific endocrine and reproductive organ in men, there may be a link between MetS and PCA risk, disease progression, and tumor invasion.As research on PCA biology continues to evolve, we understand the deep interactions between autophagy and apoptosis in prostate cancer cells. Depending on the cellular microenvironment, the complexity and multidirectionality of autophagy in tumor cells, there may be some influence in the mPCA combined with MetS (22).There are no large sample, long follow-up, retrospective study on the relationship between MetS and mPCA in China,This study is the first real-world study to report the relationship between mPCA and MetS in Xinjiang, China, and even in the Northwest. Gacci M et al (23) Meta-analysis showed that MetS was strongly associated with poorer tumor outcomes in prostate cancer, including high-grade prostate cancer (Gleason score ≥8), seminal vesicle infiltration and risk of biochemical recurrence.However, Harding J et al (24) concluded that MetS is a protective factor for prostate cancer and that men with MetS are less likely to develop prostate cancer.…”

Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer

“…Another potential new therapeutic approach, recently reviewed by Loizzo et al, is targeting autophagy to sensitize prostate cancer to other drugs ( 70 ). Autophagy has a pro-tumorigenic role by promoting survival through enabling prostate cancer cells to meet metabolic demand and avoid apoptosis.…”