Increasing evidence indicates that cancer stem cells (CSCs) and cancer stem-like cells form a special subpopulation of cells that are ubiquitous in tumors. These cells exhibit similar characteristics to those of normal stem cells in tissues; moreover, they are capable of self-renewal and differentiation, as well as high tumorigenicity and drug resistance. In prostate cancer (PCa), it is difficult to kill these cells using androgen signaling inhibitors and chemotherapy drugs. Consequently, the residual prostate cancer stem cells (PCSCs) mediate tumor recurrence and progression.

This review aims to provide a comprehensive and up-to-date overview of PCSCs, with a particular emphasis on potential therapeutic strategies targeting these cells.

After searching in PubMed and Embase databases using 'prostate cancer' and 'cancer stem cells' as keywords, studies related were compiled and examined.

In this review, we detail the origin and characteristics of PCSCs, introduce the regulatory pathways closely related to CSC survival and stemness maintenance, and discuss the link between epithelial-mesenchymal transition, tumor microenvironment and tumor stemness. Furthermore, we introduce the currently available therapeutic strategies targeting CSCs, including signaling pathway inhibitors, anti-apoptotic protein inhibitors, microRNAs, nanomedicine, and immunotherapy. Lastly, we summarize the limitations of current CSC research and mention future research directions.

A deeper understanding of the regulatory network and molecular markers of PCSCs could facilitate the development of novel therapeutic strategies targeting these cells. Previous preclinical studies have demonstrated the potential of this treatment approach. In the future, this may offer alternative treatment options for PCa patients.

Small interfering RNAs (siRNA) technology has emerged as a promising therapeutic tool for human health conditions like cancer due to its ability to regulate gene silencing. Despite FDA-approved, their delivery remains localized and limiting their systemic use. This study used single-walled carbon nanotubes (SWNTs) functionalized with polyethylene glycolated (PEGylated) phospholipids (PL-PEG) derivatives for systemic siRNA delivery. We developed an siRNA systemic delivery vehicle (SWNT-siRNA) by conjugating SWNT functionalized with PL-PEG containing either amine (PA) or maleimide (MA). The functionalized SWNT with a lower molecular weight of PA produced the SWNT-siRNA conjugate system with the highest stability and high siRNA loading quantity. The system delivered siRNA to a panel of tumour cell lines of different organs (i.e. HeLa, H1299 and MCF-7) and a non-cancerous human embryonic kidney 293 cells (HEK293T) with high biocompatibility and low toxicity. The cellular uptake of SWNT-siRNA conjugates by epithelial cells was found to be energy dependent. Importantly, the presence of P-glycoprotein, a marker for drug resistance, did not inhibit SWNT-mediated siRNA delivery. Mouse xenograft model further confirmed the potential of SWNT-siRNA conjugates with a significant gene knock-down without signs of acute toxicity. These findings pave the way for potential gene therapy applications using SWNTs as delivery vehicles.

This article focused on probing the correlation of magnetic resonance imaging (MRI) and computed tomography (CT) manifestations with biological factor expression and lymph node metastasis (LNM) in aggressive prostate cancer (PCa).

A total of 136 PCa patients underwent surgical treatment and received CT and MRI examinations before surgery, whereby the apparent diffusion coefficient (ADC) values of quantitative MRI (qMRI) parameters were obtained. Patients were categorized into the non-aggressive PCa group and the aggressive PCa group according to the postoperative pathological results and Gleason scores. The expression of biological factors (prostate-specific antigen [PSA], proliferating cell nuclear antigen [PCNA], p27, and Ki-67) in both groups was tested. CT and MRI manifestations of aggressive PCa patients were analyzed. The qMRI parameters, biological factors levels, and LNM were compared in two groups; the relationships between CT and MRI manifestations, qMRI parameters, and positive expression of biological factors and LNM were probed in two groups.

In the aggressive PCa group, MRI and CT presented different degrees of abnormal prostate changes. In the aggressive PCa group, PSA and p27 expression and ADC values were lower, and PCNA and Ki-67, and LNM rates were higher. Patients' LNM rate was higher than that of ≤2 cm when the tumor diameter was >2 cm. ADC values were positively correlated with PSA and p27 positive expression and negatively correlated with PCNA, Ki-67, and LNM in the aggressive PCa group.

MRI and CT manifestations of aggressive PCa had certain characteristics; MRI manifestations and qMRI possessed a correlation with biological factors and LNM; ADC could be employed to assess the aggressiveness of PCa.

Prostate cancer (PCa) is a significant health concern for men worldwide and is particularly prevalent in the United States. It is a complex disease presenting different molecular subtypes and varying degrees of aggressiveness. Transgenic/genetically engineered mouse models (GEMMs) greatly enhanced our understanding of the intricate molecular processes that underlie PCa progression and have offered valuable insights into potential therapeutic targets for this disease. The integration of whole-exome and whole-genome sequencing, along with expression profiling, has played a pivotal role in advancing GEMMs by facilitating the identification of genetic alterations driving PCa development. This review focuses on genetically modified mice classified into the first and second generations of PCa models. We summarize whether models created by manipulating the function of specific genes replicate the consequences of genomic alterations observed in human PCa, including early and later disease stages. We discuss cases where GEMMs did not fully exhibit the expected human PCa phenotypes and possible causes of the failure. Here, we summarize the comprehensive understanding, recent advances, strengths and limitations of the GEMMs in advancing our insights into PCa, offering genetic and molecular perspectives for developing novel GEMM models.

The natural extracellular matrix (ECM) consists of a continuous integrated fibrin network and a negatively charged proteoglycan-based matrix. In this work, we report a novel three-dimensional nanofiber hydrogel composite that mimics the natural ECM structure, exhibiting both degradability and mechanical characteristics comparable to that of tumor tissue. The embedded nanofiber improves the hydrogel mechanical properties, and varying the fiber density can match the elastic modulus of different tumor tissues (1.51-10.77 kPa). The degradability of the scaffold gives sufficient space for tumor cells to secrete and remodel the ECM. The expression levels of cancer stem cell markers confirmed the development of aggressive and metastatic phenotypes of prostate cancer cells in the 3D scaffold. Similar results were obtained in terms of anticancer resistance of prostate cancer cells in 3D scaffolds showing stem cell-like properties, suggesting that the current bionic 3D scaffold tumor model has broad potential in the development of effective targeted agents.

As the second most common cancer in men and the leading cause of cancer-related death, prostate cancer (PCa) could potentially be treated by inducing ferroptosis. In this study, we aimed to investigate whether luteolin could induce ferroptosis in PCa cells through the transcription Factor EB (TFEB).

Different concentrations of luteolin were applied to treat normal prostate epithelial cells RWPE-1 and PCa cell lines DU145, PC-3, VCaP, and LNcaP. Ferrostatin-1 (Fer-1), Necrostain-1 (Nec-1), 3-methyladenine (3-MA), chloroquine (CQ), and the apoptosis inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (Z-VAD-FMK) were added to treat DU145 and PC-3 cells. Additionally, we knocked down TFEB and performed in vitro cell experiments. Finally, tumor-forming experiments in nude mice were conducted to verify luteolin mechanism in PCa after knocking down TFEB.

There was no significant difference in RWPE-1 at 12, 24, and 48 h after treatment with 60 μM luteolin. However, a significant difference was observed between DU145 and PC-3 cells. Luteolin exhibited a promoting effect on PCa cell death. After treatment with luteolin, cell viability, and Ki67 expression were decreased, and AnV-PI-positive dead cells were increased. Fer-1, Nec-1, 3-MA, and Z-VAD-FMK reversed luteolin effects on DU145 and PC-3 cell viability, proliferation, and AnV-PI-positive dead cells. Among them, Fer-1 and 3-MA were more effective. Luteolin-induced increased autophagy and ferroptosis in DU145 and PC-3 cells. Moreover, luteolin promoted ferroptosis by inducing increased autophagy in DU145 and PC-3 cells. However, knockdown of TFEB reversed the ability of luteolin to induce lysosome degradation of ferritin. In addition, luteolin promoted PCa ferroptosis by inducing ferritinophagy in vivo.

Luteolin-induced ferroptosis in PCa cells by promoting TFEB nuclear translocation and increasing ferritinophagy.

Prostate cancer (PCa) poses a serious burden to men. Interferon-β (IFN-β) is implicated in cancer cell growth. This study hence explored the regulation of IFN-β-modified human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) in PCa cells. In vitro-cultured hUCMSCs were transfected with pcDNA3.1-IFN-β plasmid or IFN-β siRNA. hUCMSC-Exos were extracted by ultracentrifugation and identified. PCa cells (PC3 and LNCap) were treated with Exos. Cellular internalization of Exos by cells was detected by uptake assay. Cell proliferation, cycle, and apoptosis were evaluated by CCK-8, EdU staining, and flow cytometry. Levels of cell cycle-related proteins (cyclin D/cyclin E) were determined by Western blot. The effect of IFN-β-modified hUCMSC-Exos in vivo was analyzed. IFN-β-modified hUCMSC-Exos (Exooe-IFN-β or Exosi-IFN-β) were successfully isolated. IFN-β was encapsulated in Exos, and PCa cells could uptake Exos. After treating with Exooe-IFN-β, PCa cell proliferation was impeded, the percentage of cells in the G0/G1 phase, cyclin D/cyclin E levels, and cell apoptotic rate were elevated, while cells treated with Exooe-IFN-β exhibited contrary trends. IFN-β-modified hUCMSC-Exos reduced PCa tumor size and weight in vivo. Conjointly, IFN-β-modified hUCMSC-Exos suppress PCa cell proliferation and facilitate apoptosis.

Nowadays, the diagnosis and treatment system of malignant tumors has increasingly tended to be more precise and personalized while the existing tumor models are still unable to fully meet the needs of clinical practice. Notably, the emerging organoid platform has been proven to have huge potential in the field of basic-translational medicine, which is expected to promote a paradigm shift in personalized medicine. Here, given the unique advantages of organoid platform, we mainly explore the prominent role of organoid models in basic research and clinical practice from perspectives of tumor biology, tumorigenic microbes-host interaction, clinical decision-making, and regenerative strategy. In addition, we also put forward some practical suggestions on how to construct a new generation of organoid platform, which is destined to vigorously promote the reform of basic-translational medicine.

Pancreatic cancer is the leading cause of cancer mortality worldwide. Research investigating effective management strategies for pancreatic cancer is ongoing. Vitamin E, consisting of both tocopherol and tocotrienol, has demonstrated debatable effects on pancreatic cancer cells. Therefore, this scoping review aims to summarize the effects of vitamin E on pancreatic cancer. In October 2022, a literature search was conducted using PubMed and Scopus since their inception. Original studies on the effects of vitamin E on pancreatic cancer, including cell cultures, animal models and human clinical trials, were considered for this review. The literature search found 75 articles on this topic, but only 24 articles met the inclusion criteria. The available evidence showed that vitamin E modulated proliferation, cell death, angiogenesis, metastasis and inflammation in pancreatic cancer cells. However, the safety and bioavailability concerns remain to be answered with more extensive preclinical and clinical studies. More in-depth analysis is necessary to investigate further the role of vitamin E in the management of pancreatic cancers.

In the Special Issue on Prostate Cancer, we have invited 25 researchers or clinicians from prostate cancer community to review the cutting-edge topics in this field. In particular, the mini-reviews have covered various basic science and clinical aspects in prostate cancer, including prostate epithelial stem cells or progenitors, androgen and androgen receptor pathways, tumor modeling, genomics, different cell-autonomous and non-cell-autonomous mechanisms as well as various clinical issues encompassing diagnosis, risk stratification and treatments.