Prostate cancer is the most frequently diagnosed tumor of male reproductive system. Clinically, there is a lack of effective treatment drugs for prostate cancer. Previous studies have shown that AMPK inhibitor dorsomorphin was demonstrated to have potent antitumor effects. However, the effect of dorsomorphin on prostate cancer and its molecular mechanism are still unclear. In this study, the effects of dorsomorphin on the invasion and infiltration, epithelial-mesenchymal transition (EMT), and angiogenesis were investigated in two types of prostate cancer cells (DU145 and PC-3). In addition, nude mouse tumorigenic experiments were performed to confirm the antitumor effect of dorsomorphin. We found that dorsomorphin treatment concentration- and time-dependently inhibited the invasion and infiltration of DU145 and PC-3 cells. In addition, dorsomorphin reduced the expression levels of extracellular matrix components and angiogenesis-related proteins (HIF-1α and VEGF). Further study showed that dorsomorphin inhibited matrix deposition by antagonizing the EMT. Our results from nude mouse tumorigenic experiments further demonstrated dorsomorphin's tumor-growth inhibitory effect, whereas its antimetastatic potential is supported by in vitro invasion and EMT assays. Mechanistically, dorsomorphin treatment suppressed TGF-β1 expression and thereby inhibited the phosphorylation and nucleation of Smad2/3 signaling, which plays a key role in the regulation of EMT. Further study showed that dorsomorphin-triggered inactivation of JAK2/STAT3 and sonic hedgehog (Shh) signaling was involved in the inhibition of TGF-β1-mediated EMT. Interestingly, dorsomorphin inhibited the expression and nucleation of Gli1 and Gli3 but not affected the expression of Gli2. Thus, these findings reveal that the new mechanism of AMPK inhibitor dorsomorphin against prostate cancer metastasis is through synergistically antagonizing JAK2/STAT3 and Gli2-independent Shh activation.

High-intensity focused ultrasound (HIFU) is a noninvasive modality that is gaining prominence for the localized treatment of malignant tumors. Most current HIFU research utilizes mouse tumor models, where selection of appropriate mouse breed is important for conducting thermal ablation experiments on tumors with consistency. In this study, three breeds (NOD/SCID GammaC −/− (NSG), NSG-SGM3 (NSGS), and Homozygote J:NU (Nude); n = 2 per group) originating from Jackson Laboratory were tested for identifying the breed that has sufficient size for conducting HIFU experiments. Tumors were developed using a human PC3 (CRL-1435) prostate cancer cell line and monitored over 5 to 7 weeks. The surface area and volume of the implanted tumors were determined by assuming the tumor having an ellipsoidal shape. At the end of the growth period, NSG mice exhibited 29% larger tumor surface area than NSGS and 58% larger than Nude mice. Similarly, NSG mice had a 55% larger tumor volume than NSGS mice and 100% larger than Nude mice. Therefore, this research established NSG mice as the superior mouse breed for the PC3 cell–induced tumor growth having established size within a reasonable timeline (5–7 weeks). Subsequently, the NSG model with a larger sample size (n = 48) was selected for HIFU ablation, and histopathological analysis revealed a significantly higher number of apoptotic cells in the HIFU-treated tumors compared to controls. This further confirmed the model's suitability for HIFU research. Tumor surface area and volume compared between the tested (n = 2) and selected (n = 48) groups were statistically insignificant (p = 0.78 for surface area and p = 0.60 for volume).

Advancements in genotyping and sequencing technologies have driven the rapid progress in human genetics research over the last 20 years. Particularly noteworthy is the emergence of pharmacogenetic and pharmacogenomic studies, which significantly impact the advancement of precision medicine and the development of genomics-guided pharmacotherapies. Acquiring knowledge about cancer genomics holds considerable importance in understanding the biology of prostate cancer. Although progress has been made in diagnosing and treating prostate cancer, metastatic castration-resistant prostate cancer (mCRPC) remains a persistent challenge due to its poor prognosis. It is important to identify predictive biomarkers, thus enabling a personalized therapeutic approach in mCRPC patients. Therefore, biomarker-driven precision oncology allows the classification of clinically significant subtypes, the identification of prognostic and predictive biomarkers, and the development and implementation of new targeted therapies. In recent years, there has been a significant shift in the management of mCRPC, whereas novel therapeutic approaches have emerged, including PARP inhibitors, immunotherapies, theranostics, notably 177Lu-PSMA-617, and others.

Prostate cancer, a prominent malignancy impacting men worldwide, is characterized by a dynamic and intricate interplay between cancer cells and their surrounding microenvironment. The unique signature of the malignant transformation process arose from the inherent specificity of the prostate tissue and its function in semen fluid production. Unlike other cancer types where the shift to glycolytic energy supply is a hallmark of the neoplastic alteration, prostate cancer operates on entirely opposing principles. Focused on citrate production for seminal fluid, normal prostate epithelial cells function in a reduced oxidative phosphorylation (OXPHOS) manner. In the process of neoplastic transformation, cells redirect citrate into the Krebs cycle, converting inefficient to energy-efficient metabolism. From tumor initiation to metastasis, the distinct tumor microenvironment (TME), constituted of cellular and noncellular components, shapes the process of malignant transformation, rendering it increasingly aggressive, with immune system cells playing a pivotal role in connecting all these stages. This review will comprehensively elaborate the sophisticated and dynamic communication, enormous cellular plasticity and tissue flexibility leading to successive modifications of all structures, and their profound influence on disease progression.

The identification of probable sources of androgen and strategies for lowering their levels are essential to the characterization of advanced PC. The first question that can be asked during the construction of a protocol for the use of hormone therapy in prostate cancer is when, in which forms, and in which stages of prostate cancer this type of therapy can be most beneficial. The first hormone therapy for prostate cancer are LHRH agonists and LHRH antagonists. Antiandrogens are a broad class of drugs that neutralize the effects of testosterone and dihydrotestosterone, blocking androgen receptors (AR). They are used in conjunction with ADT, most frequently with LHRH agonists. Total androgen blockade (TAB) or combined androgen blockade are terms used to describe this form of treatment. The current protocols are presented based on the results of clinical investigations on a large number of patients, based on the results of main and secondary outcomes. Total androgen blockade (TAB) with the addition of antiandrogens (AR antagonists or androgen synthesis blockers) to basic ADT therapy (often LHRH antagonists) may be a “gold standard” for treating castration-resistant prostate cancer. Clinical research has demonstrated that TAB is more successful than ADT.

Prostate cancer (PCa) in most patients does not cause significant clinical symptoms, but high-risk disease, accounting for approximately 15% of PCa, has the potential to progress to a lethal phenotype. Individual approaches for assessing tumor aggressiveness and stratifying patients to reduce PCa-specific mortality while avoiding overtreatment are a great challenge. Detailed and precise histopathological examination of aggressivity in PCa, including differentiation by Gleason, perineural invasion, specific variants of PCa and tumor volume at needle or radical prostatectomy biopsies can influence therapeutic approaches. Analyses of molecular regulator proteins of the cell cycle, apoptosis, epigenetic regulators and the chemokine axis allow the assessment of tumor growth, local invasion and distant metastases and provide additional knowledge of aggressivity compared to standard markers. Current research has shown that prostate cancer stem cells, which may play a role in tumor initiation and development, disease progression, recurrence and metastasis, modification of the effect of chemotherapy and disease prognosis, are important indicators of prostate cancer aggressiveness.

Prostate cancer (PC) is one of the most common tumors in the male population. One of the possible causes of cancer is reactive oxygen species (ROS). They can be involved in all stages of tumor growth. There are a lot of different inducers of ROS. Xanthine oxidase (XO) is the enzyme that can be responsible for oxidative damage in cancer, since free radicals are also a side product of this enzyme’s activity. The results of some studies showed more than twice the activity of XO when compared to control tissue and tissue surrounding the tumor compared to control healthy tissue. It is even strongly correlated with the PSA values from the patients’ serum. This suggests XO as a potential marker in the diagnosis of the disease. The inhibition of this enzyme has been investigated as a possible direct target therapy for cancer, so it could be a theranostic marker. ROS can also participate in carcinogenesis through redox-dependent signaling pathways. The transcription factor NF-kB is a regulatory protein that controls the expression of many inducible and tissue-specific genes, thereby participating in the regulation of pro-inflammatory and immune cell responses, cell proliferation, and apoptosis. NF-κB signaling may also be crucial in tumor progression. The inhibition of signaling pathways originating from the activity of this redox-sensitive molecule could be a promising therapeutic strategy, by inhibiting the IKK subunit of NF-κB. Both ROS and NF-κB can be inducers and blockers of apoptosis. Apoptosis has an important function in the removal of damaged cells. Failure of apoptosis may be an important factor in the evolution of PC and poor response to chemotherapy and radiation therapy. The novel apoptosis inhibitors have been introduced, and they appear to have a role in prostate cancer treatment resistance. Therapeutic effect on apoptosis could be one of the possible therapies for this disease.

Aim Prostate cancer (PCa) is the second most common nonskin malignancy and the second most common cause of cancer-related deaths in men. The most common site of metastasis in PCa is the axial skeleton which may lead to back pain or pathological fractures. Hematogenous spread to the brain and involvement of the central nervous system (CNS) are a rare occurrence. However, failed androgen deprivation therapy (ADT) may facilitate such a spread resulting in an advanced metastatic stage of PCa, which carries a poor prognosis. Methods In this systematic review, we searched the PubMed, Scopus, and Web of Science online databases based on the PRISMA guideline and used all the medical subject headings (MeSH) in terms of the following search line: (“Brain Neoplasms” OR “Central Nervous System Neoplasms”) and (“Prostatic Neoplasms” OR “Prostate”). Related studies were identified and reviewed. Results A total of 59 eligible studies (902 patients) were included in this systematic review. In order to gain a deeper understanding, we extracted and presented the data from included articles based on clinical manifestations, diagnostic methods, therapeutic approaches, and prognostic status of PCa patients having BMs. Conclusion We have demonstrated the current knowledge regarding the mechanism, clinical manifestations, diagnostic methods, therapeutic approaches, and prognosis of BMs in PCa. These data shed more light on the way to help clinicians and physicians to understand, diagnose, and manage BMs in PCa patients better.

How prostate cancer is diagnosed and staged is an ever-evolving field. It plays a fundamental role in ensuring the appropriate therapeutic options are offered to the patient whilst preventing overdiagnosis and overtreatment. Despite the numerous advances in the field, a suspicion of prostate cancer continues to arise from digital rectal examination and measurement of serum prostate specific antigen (PSA). Additional derivatives of serum PSA along with urinary biomarkers and multiparametric magnetic resonance imaging can then help to risk stratify patients in order to appropriately counsel them on the risks and benefits of a prostate biopsy. After a diagnosis of prostate cancer is reached, further staging may be required and can be achieved by a variety of imaging techniques such as computed tomography (CT), bone scintigraphy, and prostate specific membrane antigen-based positron-emission tomography/CT. In this chapter, we review the current role of these and other diagnostic tools in prostate cancer.

Primary prostate tumor heterogeneity is poorly understood, leaving research efforts with challenges regarding the initiation and advancement of the disease. The growth of tumor cells is accompanied by mutations in nuclear and in mitochondrial genomes. Thus, mitochondrial DNA mutations may be used as tumor cell markers. By the use of laser capture microdissection coupled with assays for mitochondrial point mutation detection, mtDNA mutations were used to trace mutated cells at a histological level. Point mutations in mtDNA were determined in 12 primary prostate cancers. The tumors represent different pathology-prognostic grade groups. Known mutational hotspots of the mtDNA were scanned for heteroplasmy. All specimens with mtDNA heteroplasmy were subsequently subsampled by laser capture microdissection. From a total number of 1728 microsamples, mitochondrial DNA target sequences were amplified and base substitutions detected by cycling temperature capillary electrophoresis. Real-time PCR was used as a quantitative assay to determine the relative mtDNA copy number of 12 tumors studied, represented by two samples from each (N = 24); a high degree (75%) demonstrated tumor specimen heterogeneity. A grid of 96 spots isolated by laser capture microdissection demonstrated interfocal sample heterogeneity and increased the limit of detection. The spots demonstrated a wide range of mutant fractions from 0 to 100% mutant copies. The mitochondrial DNA copy number in the samples was determined by real-time PCR. No correlation between copy number and pathology-prognostic grade groups was observed. Somatic mitochondrial DNA point mutations represent traceable biomarkers demonstrating heterogeneity in primary prostate cancer. Mutations can be detected in areas before changes in tissue histopathology are evident to the pathologist.