Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies

Abstract

Prostate cancer, as one of the most prevalent malignancies in males, exhibits an approximate 5-year survival rate of 95% in advanced stages. A myriad of molecular events and mutations, including the accumulation of oncometabolites, underpin the genesis and progression of this cancer type. Despite growing research demonstrating the pivotal role of oncometabolites in supporting various cancers, including prostate cancer, the root causes of their accumulation, especially in the absence of enzymatic mutations, remain elusive. Consequently, identifying a tangible therapeutic target poses a formidable challenge. In this review, we aim to delve deeper into the implications of oncometabolite accumulation in prostate cancer. We center our focus on the consequential epigenetic alterations and impacts on cancer stem cells, with the ultimate goal of outlining novel therapeutic strategies. Graphical Abstract

Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions

“…These oncometabolites, extending their influence beyond their cells of origin, significantly impact the TME, thereby promoting processes such as tumor invasion, metastasis, and migration ( Figure 2 ). Numerous studies have demonstrated that oncometabolites can alter cellular processes and communication, leading to notable changes in gene expression, signal transduction, and overall cellular behavior, thereby playing a crucial role in cancer progression [ 35 , 36 ]. This highlights that the influence of mutp53 on metabolic pathways might drive cancer progression through the accumulation of oncometabolites, which exert a range of oncogenic effects.…”

Modulation of adipose-derived stem cell behavior by prostate pathology-associated plasma: insights from in vitro exposure

“…The expression of these molecules increases concomitantly with tumor progression and contributes to the promotion of metastasis 22 . The clinical significance of ADSCs in prostate cancer research lies in their ability to modulate the TME and thus influence the viability of tumor cells 23 – 25 . However, the role of ADSCs in prostate cancer is complex, with opposite evidence suggesting both promotional and inhibitory effects on tumor growth 26 – 28 .…”