Background: Treatment for metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) alteration remains a challenge. Recently published trials have evaluated the poly (ADP-ribose) polymerase inhibitors (PARPIs) in mCRPC. However, the efficacy in subgroup with specific HRR gene mutation and treatment protocol requires further elucidation. This meta-analysis aims to explore the efficacy of PARPIs based on subgroups and reconstructed individual patient data (IPD). Methods: Literature was searched using PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to April 2025. The primary outcome was radiographic progression-free survival (rPFS), and the secondary outcomes included overall survival (OS), prostate-specific antigen progression-free survival (PSA-PFS), and adverse events (AEs). Hazard ratios (HRs) and risk ratios (RRs) were pooled as the indicators using inverse-variance and Mantel-Haenszel methods. IPD was reconstructed from Kaplan–Meier curve. Survival analysis was performed using Cox proportional hazards model based on the reconstructed IPD. Heterogeneity was assessed by I2 and sensitivity analysis. Publication bias was examined via contour‑enhanced funnel plots. Results: Data of 1840 mCRPC patients with HRR alteration from five pivotal phase III clinical trials were analyzed. PARPIs significantly improved overall rPFS (HR: 0.55) and OS (HR: 0.85). PARPIs also prolonged rPFS across the subgroups defined by clinicopathologic features. In BRCA1/2 subgroup, survival benefits were prominent for rPFS (HR 0.32) and OS (HR 0.70). For patients with non- BRCA alterations, no benefits of PARPIs were detected for rPFS and OS in ATM subgroup, and for OS in CDK12 subgroup. Survival analyses indicated that PARPIs treatment was significantly associated with the improved rPFS (HR: 0.73, P < 0.001) and PSA-PFS (HR: 0.80, P = 0.020) in the overall population, and revealed OS benefit in BRCA1/2 subgroup (HR: 0.77, P = 0.030). Comparing with monotherapy, combination regimen of PARPIs provided greater benefits for rPFS (HR: 0.56, P < 0.001)and OS (HR: 0.64., P < 0.001). Conclusions: PARPIsimprove survival in mCRPC patients with BRCA1/2 mutation, but have no effect in those with ATM mutation. Comparing with PARPIs monotherapy, the combination regimen provides greater survival benefit in the overall population. Future investigation should validate these findings in real-world settings.

Radiopharmaceutical therapy (RPT) is a pivotal modality in cancer treatment, with its efficacy substantially modulated by the tumor microenvironment (TME). The TME regulates RPT penetration and influences therapeutic outcomes. Concurrently, RPT actively reconfigures the TME by enhancing immune activation and partially reversing immunosuppression. Specifically, RPT induces tumor cell senescence and immunogenic cell death, and catalyzes immune activation. RPT diminishes immunosuppressive elements, including regulatory T cells and tumor-associated macrophages, and augments populations of CD8⁺ T cells and natural killer cells, thereby fostering a more immunostimulatory TME. Additionally, RPT modulates critical cytokines and upregulates immune checkpoint molecules, bolstering anti-tumor immunity. Nevertheless, pathological features like hypoxia and extracellular matrix stiffness within the TME can hinder RPT biodistribution and therapeutic efficacy. Strategically targeting the TME through approaches, such as fibroblast depletion, hypoxia mitigation, metabolic reprogramming, nerve-immune-cancer interactions, or nanocarrier drug delivery, can amplify RPT effectiveness. Combination immunotherapies that integrate RPT with immune checkpoint inhibitors, chimeric antigen receptor (CAR)-T cells, or cancer vaccines have demonstrated enhanced anti-tumor responses and survival advantages in malignancies such as prostate cancer and neuroendocrine tumors. Given the complexity and heterogeneity of the TME, emerging strategies, including radiation-responsive nanocarriers, CAR-T cells engineered to secrete radiosensitizers, senolytic therapies, and artificial intelligence-driven multimodal data integration, are promising in addressing the challenges and refining precision cancer therapy. In summary, the TME serves as a critical bridge between RPT and immunotherapy; elucidating the interplay among these three elements is essential for advancing combination strategies.

Telomere, also known as a “molecular clock”, is a specific, unique cap-like structure of nucleoprotein with repetitive, noncoding, guanine-rich tandem of nucleotide sequences of DNA-protein located at the ends of chromosomes fashioned in a duplex “D-loop-T-loop” appearance. The dynamic and equilibrium of telomere homeostasis is a function of competing pro-telomere lengthening and pro-telomere shortening factors in determining the telomere length and telomerase activity. While many studies have been done on telomere dynamics, few have been done on telomeres and HIV with a stark gap in knowledge on the impact lifestyle modifications have on the telomeres of people living with HIV. Development of “telomere check kits” in the future will go a long way to put the “molecular clock” within our reach and be directly involved and aware of where we are in the “time or clock” of our life. Having extensively and comprehensively reviewed the healthy lifestyle and the improvement of telomere length and enhancement of telomerase activity that can result in promoting longevity and maximizing health-related quality of life, a full integration of lifestyle modifications as part of the management of HIV disease is long overdue.

Background: Cell line experiments remain one of the most widely used tools in preclinical cancer research. As prostate cancer cell lines underpin much of this research, evaluating their clinical relevance is essential to improve the translation of laboratory findings into patient care. Here, we assess the clinical relevance and inclusivity of 46 prostate cancer cell lines using an integrated clinical and multiomics approach. Methods: Clinical and molecular data from more than 10,000 patient cases across 24 studies in nine countries were harmonised using publicly available databases and peer-reviewed literature. Analyses included mutations, copy number alterations, structural variants, microsatellite instability, gene expression and protein expression. Clinical characteristics, including age, geographical location, ethnicity, race, cancer type, Gleason grade and metastatic stage, were evaluated to determine how well prostate cancer cell lines represent the broader patient population. Statistical comparisons were normalised and cross-validated using bioinformatics approaches. Results: Here we show that prostate cancer cell lines do not broadly represent the wider patient population and that the patients from whom these models were derived constitute a demographically and clinically biased subset. Our integrated analyses identify important gaps in the molecular and clinical diversity represented by commonly used cell lines and demonstrate differences in their suitability for modelling specific disease subtypes. Conclusions: Our findings highlight limitations in the representativeness of widely used prostate cancer cell lines and emphasise the importance of selecting models according to their clinical and molecular relevance. The proposed data-driven framework provides a practical approach for selecting more representative cell lines and has the potential to improve the translation of preclinical prostate cancer research into clinical practice.

Black men face higher prostate cancer incidence, morbidity, and mortality, yet existing preclinical models fail to reflect this disparity. This paper reviews the availability and relevance of preclinical models in representing prostate cancer in Black patients. A review of 25 studies (15,777 patients) from cBioPortal and cBioPortal GENIE, was conducted. along with a literature search across PubMed, Embase, Web of Science, and CENTRAL, to identify Black-derived cell lines. Only 36% (9/25) of studies reported racial data, with Black participants comprising just 5.18% of the studies that reported race. Cell line analysis revealed 28 Black-derived cell lines from nine individuals, highlighting a reliance on sublines, reducing biological diversity. Studies predominantly originated from the USA and lacked detailed ethnic subgroup data. This underrepresentation of Black patients restricts insights into disease mechanisms and impedes equitable care. Enhancing racial and ethnic diversity in clinical studies and preclinical models is essential for addressing these disparities.