Research progress on deep learning in magnetic resonance imaging–based diagnosis and treatment of prostate cancer: a review on the current status and perspectives

Multiparametric magnetic resonance imaging (mpMRI) has emerged as a first-line screening and diagnostic tool for prostate cancer, aiding in treatment selection and noninvasive radiotherapy guidance. However, the manual interpretation of MRI data is challenging and time-consuming, which may impact sensitivity and specificity. With recent technological advances, artificial intelligence (AI) in the form of computer-aided diagnosis (CAD) based on MRI data has been applied to prostate cancer diagnosis and treatment. Among AI techniques, deep learning involving convolutional neural networks contributes to detection, segmentation, scoring, grading, and prognostic evaluation of prostate cancer. CAD systems have automatic operation, rapid processing, and accuracy, incorporating multiple sequences of multiparametric MRI data of the prostate gland into the deep learning model. Thus, they have become a research direction of great interest, especially in smart healthcare. This review highlights the current progress of deep learning technology in MRI-based diagnosis and treatment of prostate cancer. The key elements of deep learning-based MRI image processing in CAD systems and radiotherapy of prostate cancer are briefly described, making it understandable not only for radiologists but also for general physicians without specialized imaging interpretation training. Deep learning technology enables lesion identification, detection, and segmentation, grading and scoring of prostate cancer, and prediction of postoperative recurrence and prognostic outcomes. The diagnostic accuracy of deep learning can be improved by optimizing models and algorithms, expanding medical database resources, and combining multi-omics data and comprehensive analysis of various morphological data. Deep learning has the potential to become the key diagnostic method in prostate cancer diagnosis and treatment in the future

Unleashing novel horizons in advanced prostate cancer treatment: investigating the potential of prostate specific membrane antigen-targeted nanomedicine-based combination therapy

Prostate cancer (PCa) is a prevalent malignancy with increasing incidence in middle-aged and older men. Despite various treatment options, advanced metastatic PCa remains challenging with poor prognosis and limited effective therapies. Nanomedicine, with its targeted drug delivery capabilities, has emerged as a promising approach to enhance treatment efficacy and reduce adverse effects. Prostate-specific membrane antigen (PSMA) stands as one of the most distinctive and highly selective biomarkers for PCa, exhibiting robust expression in PCa cells. In this review, we explore the applications of PSMA-targeted nanomedicines in advanced PCa management. Our primary objective is to bridge the gap between cutting-edge nanomedicine research and clinical practice, making it accessible to the medical community. We discuss mainstream treatment strategies for advanced PCa, including chemotherapy, radiotherapy, and immunotherapy, in the context of PSMA-targeted nanomedicines. Additionally, we elucidate novel treatment concepts such as photodynamic and photothermal therapies, along with nano-theragnostics. We present the content in a clear and accessible manner, appealing to general physicians, including those with limited backgrounds in biochemistry and bioengineering. The review emphasizes the potential benefits of PSMA-targeted nanomedicines in enhancing treatment efficiency and improving patient outcomes. While the use of PSMA-targeted nano-drug delivery has demonstrated promising results, further investigation is required to comprehend the precise mechanisms of action, pharmacotoxicity, and long-term outcomes. By meticulous optimization of the combination of nanomedicines and PSMA ligands, a novel horizon of PSMA-targeted nanomedicine-based combination therapy could bring renewed hope for patients with advanced PCa

Efficient Delivery of Therapeutic siRNA with Nanoparticles Induces Apoptosis in Prostate Cancer Cells

Gene silencing using small interfering RNA (siRNA) has shown significant potential in the treatment of cancer. Herein, we developed the lipid-polymer hybrid nanoparticles (PEG-LP/siRNA NPs) for siRNA delivery. The cell viability assay indicated that PEG-LP/siRNA NPs had negligible cell cytotoxicity. The cellular uptake efficiency of PEG-LP/siRNA NPs measured by flow cytometry was up to 94.4%. Importantly, in vitro gene knockdown experiments demonstrated that PEG-LP/siJnk-1 NPs could significantly downregulate the expression of Jnk-1 at both the mRNA and protein levels in DU145 cells. Gene knockdown of Jnk-1 could activate apoptosis in part by the mitochondrial pathway in DU145 cells. Moreover, the PEG-LP/siJnk-1 NPs could inhibit tumor growth in a DU145 xenograft murine model, suggesting its therapeutic promise in cancer therapy

Efficient Delivery of Therapeutic siRNA with Nanoparticles Induces Apoptosis in Prostate Cancer Cells

Gene silencing using small interfering RNA (siRNA) has shown significant potential in the treatment of cancer. Herein, we developed the lipid-polymer hybrid nanoparticles (PEG-LP/siRNA NPs) for siRNA delivery. The cell viability assay indicated that PEG-LP/siRNA NPs had negligible cell cytotoxicity. The cellular uptake efficiency of PEG-LP/siRNA NPs measured by flow cytometry was up to 94.4%. Importantly, in vitro gene knockdown experiments demonstrated that PEG-LP/siJnk-1 NPs could significantly downregulate the expression of Jnk-1 at both the mRNA and protein levels in DU145 cells. Gene knockdown of Jnk-1 could activate apoptosis in part by the mitochondrial pathway in DU145 cells. Moreover, the PEG-LP/siJnk-1 NPs could inhibit tumor growth in a DU145 xenograft murine model, suggesting its therapeutic promise in cancer therapy

Metadherin is an apoptotic modulator in prostate cancer through miR-342-3p regulation

Prostate cancer is the second most common cancer in men worldwide. This study focused to clarify the roles of Metadherin (MTDH) and miR-342-3p in prostate cancer. We identified that MTDH was up-regulated and miR-342-3p was down-regulated in the prostate tissues, and there is an inverse correlation between MTDH and miR-342-3p. Functional studies revealed that miR-342-3p directly targets MTDH via binding to the 3′ untranslated regions (UTRs) in the prostate cancer cells. Moreover, we also found MTDH overexpression in DU145 and PC3 cells inhibited apoptosis. Subsequently, miR-342-3p has been revealed to reverse the MTDH effect on the cellular apoptosis in the further studies. Our results indicate that MTDH repress apoptosis of prostate cancer in vitro and provides a new strategy for human prostate cancer therapy in the future. Keywords: MTDH, miR-342-3p, Apoptosi

DataSheet1_Systemic triplet therapy for metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis.PDF

Purpose: To perform a systematic review and network meta-analysis to compare the efficacy and safety of currently available docetaxel-based systemic triplet therapies for metastatic hormone-sensitive prostate cancer (mHSPC).Methods: We searched for eligible publications in PubMed, Embase, and Cochrane CENTRAL. Improvements in overall survival (OS) and radiographic progression-free time (rPFS) were compared indirectly using network meta-analysis and evaluated using the surface under the cumulative ranking curve (SUCRA). Other secondary endpoints, such as time to castration-resistant prostate cancer and/or adverse events (AEs), were also compared and evaluated.Results: Five trials were selected and analyzed using a network meta-analysis. Compared to androgen deprivation therapy (ADT) plus docetaxel, darolutamide (hazard ratio [HR]: 0.68, 95% credible interval [CrI]: 0.57–0.80) and abiraterone (HR: 0.75, 95% CrI: 0.59–0.95) triplet therapy had significantly longer OS, and darolutamide triplet therapy was the first treatment ranked. Abiraterone (HR: 0.49, 95% CrI: 0.39–0.61) and enzalutamide (HR: 0.52, 95% CrI: 0.30–0.89) had significantly better rPFS than ADT plus docetaxel; however, all three therapies, including abiraterone, apalutamide, and enzalutamide, were the best options with a similar SUCRA. At most secondary endpoints, systemic triplet therapy was superior to ADT plus docetaxel. The risk of any AEs in darolutamide or abiraterone triplet therapy was comparable with ADT plus docetaxel (odds ratio [OR]: 2.53, 95% credible interval [CrI]: 0.68–12.63; OR: 1.07, 95% CrI: 0.03–36.25). Abiraterone triplet therapy had an increased risk of grade≥3 AEs (OR: 1.56, 95% CrI: 1.15–2.11).Conclusion: Systemic triplet therapy was more effective than ADT plus docetaxel for mHSPC. Of the triplet therapy regimens, darolutamide ranked first in terms of improved OS. Abiraterone and enzalutamide triplet ranked first in terms of rFPS, however, it did not confer a statistically difference among all triplet regimens. The overall risk of AEs was comparable. More studies are required for current and potential combinations of systemic triplet therapy.</p

DataSheet2_Systemic triplet therapy for metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis.pdf

Purpose: To perform a systematic review and network meta-analysis to compare the efficacy and safety of currently available docetaxel-based systemic triplet therapies for metastatic hormone-sensitive prostate cancer (mHSPC).Methods: We searched for eligible publications in PubMed, Embase, and Cochrane CENTRAL. Improvements in overall survival (OS) and radiographic progression-free time (rPFS) were compared indirectly using network meta-analysis and evaluated using the surface under the cumulative ranking curve (SUCRA). Other secondary endpoints, such as time to castration-resistant prostate cancer and/or adverse events (AEs), were also compared and evaluated.Results: Five trials were selected and analyzed using a network meta-analysis. Compared to androgen deprivation therapy (ADT) plus docetaxel, darolutamide (hazard ratio [HR]: 0.68, 95% credible interval [CrI]: 0.57–0.80) and abiraterone (HR: 0.75, 95% CrI: 0.59–0.95) triplet therapy had significantly longer OS, and darolutamide triplet therapy was the first treatment ranked. Abiraterone (HR: 0.49, 95% CrI: 0.39–0.61) and enzalutamide (HR: 0.52, 95% CrI: 0.30–0.89) had significantly better rPFS than ADT plus docetaxel; however, all three therapies, including abiraterone, apalutamide, and enzalutamide, were the best options with a similar SUCRA. At most secondary endpoints, systemic triplet therapy was superior to ADT plus docetaxel. The risk of any AEs in darolutamide or abiraterone triplet therapy was comparable with ADT plus docetaxel (odds ratio [OR]: 2.53, 95% credible interval [CrI]: 0.68–12.63; OR: 1.07, 95% CrI: 0.03–36.25). Abiraterone triplet therapy had an increased risk of grade≥3 AEs (OR: 1.56, 95% CrI: 1.15–2.11).Conclusion: Systemic triplet therapy was more effective than ADT plus docetaxel for mHSPC. Of the triplet therapy regimens, darolutamide ranked first in terms of improved OS. Abiraterone and enzalutamide triplet ranked first in terms of rFPS, however, it did not confer a statistically difference among all triplet regimens. The overall risk of AEs was comparable. More studies are required for current and potential combinations of systemic triplet therapy.</p

Chimeric antigen receptor-modified T cells therapy in prostate cancer: A comprehensive review on the current state and prospects

Recent immunotherapy research has focused on chimeric antigen receptor-modified T cells (CAR-Ts). CAR-T therapies have been clinically applied to manage hematologic malignancies with satisfactory effectiveness. However, the application of CAR-T immunotherapy in solid tumors remains challenging. Even so, current CAR-T immunotherapies for prostate cancer (PCa) have shown some promise, giving hope to patients with advanced metastatic PCa. This review aimed to elucidate different types of prostate tumor-associated antigen targets, such as prostate-specific membrane antigen and prostate stem cell antigen, and their effects. The current status of the corresponding targets in clinical research through their applications was also discussed. To improve the efficacy of CAR-T immunotherapy, we addressed the possible applications of multimodal immunotherapy, chemotherapy, and CAR-T combined therapies. The obstacles of solid tumors were concisely elaborated. Further studies should aim to discover novel potential targets and establish new models by overcoming the inherent barriers of solid tumors, such as tumor heterogeneity and the immunosuppressive nature of the tumor microenvironment