Decoding the heterogeneous landscape in the development prostate cancer (Review)

Abstract

Prostate cancer (PCa) is characterized as being histologically and molecularly heterogeneous; however, this is not only incorrect among individuals, but also at the multiple foci level, which originates in the prostate gland itself. The reasons for such heterogeneity have not been fully elucidated; however, understanding these may be crucial in determining the course of the disease. PCa is characterized by a complex network of chromosomal rearrangements, which simultaneously deregulate multiple genes; this could explain the appearance of exclusive events associated with molecular subtypes, which have been extensively investigated to establish clinical management and the development of therapies targeted to this type of cancer. From a clinical aspect, the prognosis of the patient has focused on the characteristics of the index lesion (the largest focus in PCa); however, a significant percentage of patients (11%) also exhibit an aggressive secondary foci, which may determine the prognosis of the disease, and could be the determining factor of why, in different studies, the classification of the subtypes does not have an association with prognosis. Due to the aforementioned reasons, the analysis of molecular subtypes in several foci, from the same individual could assist in determining the association between clinical evolution and management of patients with PCa. Castration-resistant PCa (CRPC) has the worst prognosis and develops following androgen ablation therapy. Currently, there are two models to explain the development of CRPC: i) The selection model and ii) the adaptation model; both of which, have been found to include alterations described in the molecular subtypes, such as Enhancer of zeste 2 polycomb repressive complex 2 subunit overexpression, isocitrate dehydrogenase (NAPD + )1 and forkhead box A1 mutations, suggesting that the presence of specific molecular alterations could predict the development of CRPC. This type of analysis could lead to a biological understanding of PCa, to develop personalized medicine strategies, which could improve the response to treatment thus, avoiding the development of resistance. Therefore, the present review discusses the primary molecular factors, to which variable heterogeneity in PCa progress has been attributed. Contents 1. Introduction 2. Molecular heterogeneity of PCa 3. Molecular progression to CRPC 4. Conclusions

Identification of Metabolism-Related Gene-Based Subgroup in Prostate Cancer

“…Other treatment methods, such as hormone therapy and chemoradiotherapy, are not satisfactory for the prognosis ( 7 ). In addition, PCa has high heterogeneity, which results in different prognoses of patients after treatment ( 8 ). Therefore, there is a need to deeply understand the potential mechanism leading to PCa progression and metastasis, and select specific subtypes to find the population who benefit the most.…”

Does Perioperative Testosterone Predict Post-Prostatectomy Genomic Risk Score?

“…Moreover, commercial prostate cancer diagnostic kits like the Decipher assay examine the index tumor; however, this approach can miss identification of some aggressive tumors due to intratumoral and intertumoral heterogeneity. 25 Finally, the short followup period of this cohort represents another limitation. Despite these limitations, this is the first study to assess the correlation of preoperative testosterone levels on the tumor transcriptome and showed no significant clinical correlation between pre-defined GC score risk groups and the testosterone group.…”