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Open research questions in Prostate Cancer Treatment and Research

714 gap statements mined from Prostate Cancer Treatment and Research papers in our 7.9M-paper local library, which holds 3,252 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Limited real-world data on the use of zoledronic acid in resource-limited settings, particularly in sub-Saharan Africa. Need for studies on the clinical outcomes and safety of zoledronic acid in patients with metastatic castration-resistant prostate cancer and bone metastases.

    Clinical outcomes and safety of zoledronic acid in castration-resistant metastatic prostate cancer with bone metastases: real-world data from Côte d’Ivoire · 2026 · DOI

  • The semi-quantitative nature of immunohistochemistry may lack precision. Interobserver variability may occur in the evaluation of stained sections. The study has a limited sample size of 77 patients.

    PTEN and ERG Biomarkers as Predictors of Biochemical Recurrence Risk in Patients Undergoing Radical Prostatectomy · 2025 · DOI

  • Limited studies on the pharmacological activity of pyripyropene O. Need for novel and efficient therapeutic targets for prostate cancer. Limited understanding of the mechanism of action of pyripyropene O on prostate cancer cells.

    Targeting YY1-DR5 Axis by Pyripyropene O as a Novel Therapeutic Strategy Against Prostate Cancer: Molecular Mechanisms and In Vivo Zebrafish Validation · 2025 · DOI

  • The molecular mechanisms underlying progression from metastatic hormone‐sensitive prostate cancer (mHSPC) to metastatic castration‐resistant prostate cancer (mCRPC) remain incompletely understood.

    The VCPIP1‐UBE3A Deubiquitination‐Ubiquitination Cascade Contributes to Castration‐Resistant Prostate Cancer Progression · 2026 · DOI

  • The effectiveness and safety of radium-223 (Ra-223) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastasis in real-world clinical practice in China remain to be fully examined.

    Real-world effectiveness and safety of radium-223 therapy in castration-resistant prostate cancer with bone metastases · 2026 · DOI

  • While androgen deprivation therapy (ADT) is used in this setting, its impact on metastatic disease outcomes remains unclear in contemporary population-based cohorts.

    Progression to castration-resistance and metastatic disease following androgen deprivation therapy for biochemical recurrence after prostate cancer surgery · 2026 · DOI

  • Metabolic alterations are a hallmark of cancer, yet their direct influence on oncogenic splicing remains unclear.

    Metabolic reprogramming promotes AR-V7 splicing via SRSF2 lactylation in castration-resistant prostate cancer · 2026 · DOI

  • However, the benefit of combining triplet therapy with local surgery remains unclear and warrants further investigation in the present study.

    Evaluation of triplet therapy combined with robot‐assisted cytoreductive prostatectomy for high‐volume metastatic prostate cancer: a multicentre randomised controlled trial protocol · 2026 · DOI

  • Only a small subset of patients (~5%) with mismatch repair deficiency, high microsatellite instability, or high tumour mutational burden derive limited benefit and responses remain insufficiently durable.

    Why immunotherapy fails in prostate cancer and what comes next · 2026 · DOI

  • However, in prostate cancer (PCa), the mechanisms underlying TMB elevation and its prognostic utility across diverse treatment regimens remain poorly understood.

    Comprehensive Analysis of Tumor Mutational Burden in Prostate Cancer: Multipublic Dataset Analysis · 2026 · DOI

  • In this narrative review, SBRT was associated with clinically relevant observed intervals before systemic treatment change in carefully selected patients, but the magnitude of benefit directly attributable to SBRT remains uncertain in the absence of randomized comparators.

    Oligoprogressive Prostate Cancer: Can Metastasis-Directed Therapy Prolong the Benefit of Systemic Treatment? · 2026 · DOI

  • Dose reduction is often considered for enzalutamide-associated fatigue and appetite loss, but within-patient changes in serum concentrations and patient-reported symptoms before and after dose reduction following symptom onset remain insufficiently characterized.

    Within-patient changes in serum concentrations and patient-reported outcomes following symptom-guided enzalutamide dose reduction from 160 to 120 mg · 2026 · DOI

  • Tryptophan metabolism (TM) participates in regulating tumor immunity and malignant progression, yet its prognostic relevance in PCa remains poorly characterized.

    Tryptophan metabolism-derived prognostic signature: A potential biomarker for risk stratification and exploratory immunotherapy relevance analysis in prostate cancer · 2026 · DOI

  • Despite characterization of androgen pathways, the broader intraprostatic steroid environment remains underexplored.

    Intraprostatic steroid hormones and endocrine disruptors in prostate cancer · 2026 · DOI

  • TBRG4 has been implicated in the progression of several malignancies, but its biological function and clinical relevance in prostate cancer remain unclear.

    The clinical and biological significance of TBRG4 expression in prostate cancer · 2026 · DOI

  • Dexamethasone (DEX), a glucocorticoid receptor agonist, is widely used for prostate cancer therapies, although its exact impact on androgen-independent prostate cancer cells remains unclear.

    The impact of dexamethasone on cellular stress responses caused by mild serum deprivation in androgen-insensitive prostate cancer cells · 2025 · DOI

  • The potential synergy of BiTEs with immune checkpoint inhibitors and tumor microenvironment-modulating agents should be further explored to enhance therapeutic efficacy.

    PSMA-based Therapies and Novel Therapies in Advanced Prostate Cancer: The Now and the Future · 2025 · DOI

  • Despite its importance, the precise mechanisms by which the NTD regulates AR's DNA-binding activity remain incompletely understood.

    Deciphering the allosteric control of androgen receptor DNA binding by its disordered N-terminal domain · 2025 · DOI

  • The study challenges the existence of an AR-V specific transcriptome responsible for treatment resistance and tumor progression and highlights the need for further investigation into the molecular mechanism by which AR-V proteins route resistance to ARTA treatment.

    Comprehensive analysis of androgen receptor splice variant target gene expression in prostate cancer · 2025 · DOI

  • While genomic alterations in high-risk and locally advanced cases may signal early progression or micrometastatic disease, their clinical finding and utility remains underexplored.

    A novel comprehensive cancer genome profiling for non‐metastatic prostate cancer: study protocol with FPG500 to detect actionable alterations representative of progressive disease · 2025 · DOI

  • The public dataset does not provide validated AR-V7 status at the patient or single-cell level, - The study is a secondary bioinformatics analysis of publicly available scRNA-seq data, - The dataset is cross-sectional, and pseudotime represents a computational ordering of cell states and not longitudinal follow-up of individual tumor cells, - The study lacks direct clinical AR-V7 measurements, - The study does not…

    Androgen receptor signaling at the tumor-immune interface in castration-resistant prostate cancer: single-cell transcriptomic analysis with AR-V7-related RT-qPCR context · 2026 · DOI

  • Functional perturbation studies are required to establish AR-V7-specific causality or clinical prediction, - Datasets with directly measured AR-V7 status are needed to validate the findings, - Further research into the role of AR-V7 in CRPC is necessary, - Studies examining the tumor-immune microenvironment in CRPC…

    Androgen receptor signaling at the tumor-immune interface in castration-resistant prostate cancer: single-cell transcriptomic analysis with AR-V7-related RT-qPCR context · 2026 · DOI

  • The semi-quantitative nature of immunohistochemistry may lack the precision of molecular assays - Potential interobserver variability was addressed by applying standardized cutoffs and ensuring independent scoring by two…

    PTEN and ERG Biomarkers as Predictors of Biochemical Recurrence Risk in Patients Undergoing Radical Prostatectomy · 2025 · DOI

  • These findings identify a VCPIP1/UBE3A deubiquitination–ubiquitination cascade contributing to CRPC progression and support further investigation of VCPIP1 as a potential prognostic biomarker and therapeutic target.

    The VCPIP1‐UBE3A Deubiquitination‐Ubiquitination Cascade Contributes to Castration‐Resistant Prostate Cancer Progression · 2026 · DOI

  • To describe the incidence, characteristics and mortality of men who present with complications of metastatic prostate cancer, a previously under-reported population.

    Characteristics and outcomes of men presenting with complications of metastatic prostate cancer · 2026 · DOI

Most-cited papers in Prostate Cancer Treatment and Research

Most recent work

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Open questions raised by papers listed on this page include: (1) The molecular mechanisms underlying progression from metastatic hormone‐sensitive prostate cancer (mHSPC) to metastatic castration‐resistant prostate cancer (mCRPC) remain incompletely understood (“The VCPIP1‐UBE3A Deubiquitination‐Ubiquitination Cascade Contributes to…”, 2026); (2) The effectiveness and safety of radium-223 (Ra-223) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastasis in real-world clinical practice in China remain to be fully examined (“Real-world effectiveness and safety of radium-223 therapy in…”, 2026); (3) While androgen deprivation therapy (ADT) is used in this setting, its impact on metastatic disease outcomes remains unclear in contemporary population-based cohorts (“Progression to castration-resistance and metastatic disease following androgen…”, 2026); (4) Metabolic alterations are a hallmark of cancer, yet their direct influence on oncogenic splicing remains unclear (“Metabolic reprogramming promotes AR-V7 splicing via SRSF2 lactylation in…”, 2026); (5) In prostate cancer (PCa), the mechanisms underlying TMB elevation and its prognostic utility across diverse treatment regimens remain poorly understood (“Comprehensive Analysis of Tumor Mutational Burden in Prostate Cancer:…”, 2026). 714 gap statements have been mined from Prostate Cancer Treatment and Research papers in our 7.9M-paper local library, which holds 3,252 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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