Androgen deprivation therapy-resistant club cells are linked to myeloid cell-driven immunosuppression in the prostate tumor microenvironment DOI Open Access
Antti Kiviaho, Sini K. Eerola, Heini Kallio

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 28, 2024

Abstract Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated mechanisms through which cells escape treatment, but their relation toward tumor microenvironment (TME) remains elusive. Here we present comprehensive landscape of prostate TME at multiple points in standard timeline employing single-cell RNA-sequencing spatial transcriptomics data from 110 patients. We identify club-like as key epithelial cell subtype that acts an interface between immune system. Tissue areas enriched with depleted androgen signaling upregulated expression luminal progenitor markers. Club-like display senescence-associated secretory phenotype presence linked to increased polymorphonuclear myeloid-derived suppressor (PMN-MDSC) activity. Our results indicate partake inducing myeloid inflammation previously associated deprivation therapy resistance, providing rationale for therapeutic targeting.

Language: Английский

Advancements in proteogenomics for preclinical targeted cancer therapy research DOI Creative Commons

Yuying Suo,

Yuanli Song, Yuqiu Wang

et al.

Biophysics Reports, Journal Year: 2025, Volume and Issue: 11(1), P. 56 - 56

Published: Jan. 1, 2025

Advancements in molecular characterization technologies have accelerated targeted cancer therapy research at unprecedented resolution and dimensionality. Integrating comprehensive multi-omic profiling of a tumor, proteogenomics, marks transformative milestone for preclinical research. In this paper, we initially provided an overview proteogenomics research, spanning genomics, transcriptomics, proteomics. Subsequently, the applications were introduced examined from different perspectives, including but not limited to genetic alterations, quantifications, single-cell patterns, post-translational modification levels, subtype signatures, immune landscape. We also paid attention combined multi-omics data analysis pan-cancer analysis. This paper highlights crucial role elucidating mechanisms tumorigenesis, discovering effective therapeutic targets promising biomarkers, developing subtype-specific therapies.

Language: Английский

Citations

0
Multidimensional single-cell analysis: Diverse strategies and emerging applications in the life sciences DOI
Boyang Zhang,

Xinyue Lan,

Siyuan Tan

et al.

TrAC Trends in Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 118170 - 118170

Published: Jan. 1, 2025

Language: Английский

Citations

0
Comparative transcriptomics reveals a mixed basal, club, and hillock epithelial cell identity in castration-resistant prostate cancer DOI Creative Commons
Samuel P. Pitzen,

Amber N. Rudenick,

Yinjie Qiu

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(6)

Published: Feb. 6, 2025

Inhibiting the androgen receptor (AR) is effective for treatment of advanced prostate cancers because their AR-dependent luminal epithelial cell identity. Tumors progress during therapy to castration-resistant cancer (CRPC) by restoring AR signaling and maintaining identity or converting through lineage plasticity a neuroendocrine (NE) double-negative CRPC (DNPC) lacking NE identities. Here, we show that DNPC cells express genes defining basal, club, hillock from benign prostate. We identified KLF5 as regulator this mixed in models. KLF5-mediated upregulation RARG uncovered sensitivity growth inhibition retinoic acid agonists, which down-regulated up-regulated AR. These findings offer classifications based on identities nominate therapeutic targets displaying

Language: Английский

Citations

0
Overcoming drug resistance in castrate-resistant prostate cancer: current mechanisms and emerging therapeutic approaches DOI Open Access
Adam Khorasanchi, Feng Hong, Yuanquan Yang

et al.

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Metastatic castration-resistant prostate cancer (mCRPC) is driven by a complex network of resistance mechanisms against standard-of-care therapies, resulting in poor long-term outcomes. This review offers uniquely comprehensive and integrative perspective on these pathways, systematically examining both androgen receptor (AR)-dependent factors (including AR overexpression, point mutations, glucocorticoid signaling, splice variants, post-translational modifications, altered coregulators, intratumoral hormone biosynthesis) AR-independent pathways (such as neuroendocrine differentiation, lineage plasticity, alternative growth factor signaling). We also highlight influencing immunotherapy, chemotherapy, radiopharmaceutical therapy targeted therapy. By synthesizing emerging insights across domains, this not only clarifies the underlying biology mCRPC but identifies key leverage points for more effective interventions. Building foundation, we propose forward-looking framework overcoming drug resistance, emphasizing importance biomarker-guided patient selection, combination strategies that simultaneously target multiple mechanisms, novel therapies under investigation. These recommendations are intended to guide future clinical trial designs research priorities move beyond incremental improvements. Ultimately, synthesis aims serve resource clinicians researchers accelerate development durable, precision-based treatment mCRPC.

Language: Английский

Citations

0
Integrative multi-omics analysis and machine learning refine global histone modification features in prostate cancer DOI Creative Commons
Xiaofeng He, Qintao Ge, Weihao Zhao

et al.

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: March 12, 2025

Background Prostate cancer (PCa) is a major cause of cancer-related mortality in men, characterized by significant heterogeneity clinical behavior and treatment response. Histone modifications play key roles tumor progression resistance, but their regulatory effects PCa remain poorly understood. Methods We utilized integrative multi-omics analysis machine learning to explore histone modification-driven PCa. The Comprehensive Machine Learning Modification Score (CMLHMS) was developed classify into two distinct subtypes based on modification patterns. Single-cell RNA sequencing performed, drug sensitivity identified potential therapeutic vulnerabilities. Results High-CMLHMS tumors exhibited elevated activity, enriched proliferative metabolic pathways, were strongly associated with castration-resistant prostate (CRPC). Low-CMLHMS showed stress-adaptive immune-regulatory phenotypes. revealed differentiation trajectories related aggressiveness Drug that high-CMLHMS more responsive growth factor kinase inhibitors (e.g., PI3K, EGFR inhibitors), while low-CMLHMS demonstrated greater cytoskeletal DNA damage repair-targeting agents Paclitaxel, Gemcitabine). Conclusion CMLHMS model effectively stratifies unique biological characteristics. This study provides new insights suggests targets, contributing precision oncology strategies for advanced

Language: Английский

Citations

0
Exploring the impact of cuproptosis on prostate cancer prognosis via RNA methylation regulation based on single cell and bulk RNA sequencing data DOI Creative Commons
Junchao Wu,

Wentian Wu,

Jiaxuan Qin

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 1, 2025

Cuproptosis, along with RNA methylation regulators, has recently come to the fore as innovative mechanisms governing cell death, exerting profound impact on onset and progression of multiple cancers. Nonetheless, prognostic implications underlying regulatory them associated prostate cancer (PCa) remain be thoroughly investigated. Genomic clinical data for PCa from The Cancer Genome Atlas datasets were analyzed identify a model through univariate Least Absolute Shrinkage Selection Operator Cox regression analyses that validated utilizing external datasets. We used receiver operating characteristic curves C-index evaluate accuracy our model. In conjunction this, we conducted single-cell sequencing (scRNA-seq) investigate degree immune infiltration, well assess patients' responses diverse chemotherapy agents. Especially, qPCR assay was utilized unveil expression signature genes in PCa. meticulously selected six Cuproptosis-Associated Methylation Regulators (CARMRs) establish risk prognosis model, which further verified obtain enhanced predictive capacity validation cohorts. Insights infiltration scRNA-seq have elucidated characteristics PCa, highlighted immunosuppressive role T cells response. Additionally, drug susceptibility analysis demonstrated patients low-risk category derived better benefit bicalutamide treatment, whereas those high-risk group exhibited favor response adriamycin docetaxel treatments. immunohistochemistry (IHC) staining assays also reveal dramatically altered pattern TRDMT1 ALYREF tissues. general, established involving CARMRs can predict recurrence identified possible affecting progression, thereby promoting research this field.

Language: Английский

Citations

0
Comprehensive Integrated Analysis Reveals the Spatiotemporal Microevolution of Cancer Cells in Patients with Bone-Metastatic Prostate Cancer DOI Creative Commons
Yinghua Feng, Xiuli Zhang, Guangpeng Wang

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 909 - 909

Published: April 9, 2025

Background/Objectives: Bone metastasis is a frequent and life-threatening event in advanced cancers, affecting up to 70–85% of prostate cancer patients. Understanding the cellular molecular mechanisms underlying bone essential for developing targeted therapies. This study aimed systematically characterize heterogeneity microenvironmental adaptation metastases using single-cell transcriptomics. Methods: We integrated largest transcriptome dataset date, encompassing 124 samples from primary tumors, various metastatic sites, non-malignant tissues (e.g., benign prostatic hyperplasia, normal marrow). After quality control, 602,497 high-quality transcriptomes were analyzed. employed unsupervised clustering, gene expression profiling, mutation analysis, metabolic pathway reconstruction cell subtypes tumor remodeling. Results: Cancer epithelial cells dominated microenvironment but exhibited pronounced heterogeneity, posing challenges conventional clustering methods. By integrating genetic features, we revealed key evolutionary trajectories during metastasis. Notably, identified novel subpopulation, NEndoCs, characterized by unique differentiation patterns distinct spatial distribution across niches. also observed significant reprogramming recurrent mutations linked prostate-to-bone transitions. Conclusions: comprehensively elucidates patterns, reprogramming, cancer, providing targets clinical strategies precise treatment cancer.

Language: Английский

Citations

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Single-cell sequencing unveils the transcriptomic landscape of castration-resistant prostate cancer-associated fibroblasts and their association with prognosis and immunotherapy response DOI Creative Commons
Yi‐Feng Qiu, Yuhan Wang,

Jiahe Liu

et al.

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 30, 2025

Language: Английский

Citations

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Development of a machine learning-based predictive risk model combining fatty acid metabolism and ferroptosis for immunotherapy response and prognosis in prostate cancer DOI Creative Commons

Zepeng Wang,

Zhihong Dai,

Yuren Gao

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 12, 2025

Language: Английский

Citations

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Bolstering CD8+ T Cells’ Antitumor Immunity: A Promising Strategy to Improve the Response to Advanced Prostate Cancer Treatment DOI Creative Commons

Buyun Dang,

Lixin Liang,

Zhijun Li

et al.

Biology, Journal Year: 2025, Volume and Issue: 14(5), P. 544 - 544

Published: May 14, 2025

Prostate cancer is among the most frequently diagnosed and deadly cancers men in Western world. It typically classified as an immune “cold” tumor due to its sparse cell presence limited immunogenic response. Recent research has revealed significant role of cells, especially CD8+ T both prostate progression treatment efficacy. This review integrates recent findings provide a comprehensive overview current understanding dynamics discusses emerging strategies improve outcomes. The ongoing exploration new molecular targets development innovative immunotherapeutic approaches hold promise for more effective management cancer, particularly context advanced resistant forms disease.

Language: Английский

Citations

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