AI Article Synopsis
- - Researchers found that HER3, a protein often overexpressed in aggressive prostate cancer, is linked to faster progression to castration resistance and lower survival rates.
- - The study identified that NRG1, a ligand for HER3, is primarily produced by certain immune cells in the tumor environment, and its presence promotes cancer cell growth.
- - Targeting HER3 with specific therapies, like the antibody-drug conjugate U3-1402, shows promise in fighting HER3-positive prostate cancer, suggesting the need for further clinical trials.
Article Abstract
It has been recognized for decades that ERBB signaling is important in prostate cancer, but targeting ERBB receptors as a therapeutic strategy for prostate cancer has been ineffective clinically. However, we show here that membranous HER3 protein is commonly highly expressed in lethal prostate cancer, associating with reduced time to castration resistance (CR) and survival. Multiplex immunofluorescence indicated that the HER3 ligand NRG1 is detectable primarily in tumor-infiltrating myelomonocytic cells in human prostate cancer; this observation was confirmed using single-cell RNA sequencing of human prostate cancer biopsies and murine transgenic prostate cancer models. In castration-resistant prostate cancer (CRPC) patient-derived xenograft organoids with high HER3 expression as well as mouse prostate cancer organoids, recombinant NRG1 enhanced proliferation and survival. Supernatant from murine bone marrow-derived macrophages and myeloid-derived suppressor cells promoted murine prostate cancer organoid growth , which could be reversed by a neutralizing anti-NRG1 antibody and ERBB inhibition. Targeting HER3, especially with the HER3-directed antibody-drug conjugate U3-1402, exhibited antitumor activity against HER3-expressing prostate cancer. Overall, these data indicate that HER3 is commonly overexpressed in lethal prostate cancer and can be activated by NRG1 secreted by myelomonocytic cells in the tumor microenvironment, supporting HER3-targeted therapeutic strategies for treating HER3-expressing advanced CRPC. SIGNIFICANCE: HER3 is an actionable target in prostate cancer, especially with anti-HER3 immunoconjugates, and targeting HER3 warrants clinical evaluation in prospective trials.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932336 | PMC |
| http://dx.doi.org/10.1158/0008-5472.CAN-21-3360 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Comparison of baseline global gene expression profiles of prostate cancer cell lines LNCaP and DU145.
BMC Res Notes
December 2024
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
Introduction: DU145 and LNCaP are classic prostate cancer cell lines. Characterizing their baseline transcriptomics profiles (without any intervention) can offer insights into baseline genetic features and oncogenic pathways that should be considered while interpreting findings after various experimental interventions such as exogenous gene transfection or drug treatment.
Methods: LNCaP and DU145 cell lines were cultured under normal conditions, followed by RNA extraction, cDNA conversion, library preparation, and RNA sequencing using the Illumina NovaSeq platform.
Unveiling the molecular profile of a prostate carcinoma: implications for personalized medicine.
Biol Direct
December 2024
Urology Unit, Department of Surgery, Tor Vergata University of Rome, Rome, Italy.
Background: Prostate cancer is the most common diagnosed tumor and the fifth cancer related death among men in Europe. Although several genetic alterations such as ERG-TMPRSS2 fusion, MYC amplification, PTEN deletion and mutations in p53 and BRCA2 genes play a key role in the pathogenesis of prostate cancer, specific gene alteration signature that could distinguish indolent from aggressive prostate cancer or may aid in patient stratification for prognosis and/or clinical management of patients with prostate cancer is still missing. Therefore, here, by a multi-omics approach we describe a prostate cancer carrying the fusion of TMPRSS2 with ERG gene and deletion of 16q chromosome arm.
View Article and Find Full Text PDFInfectious complications following transperineal prostate biopsy with or without periprocedural antibiotic prophylaxis-a systematic review including meta-analysis of all comparative studies.
Prostate Cancer Prostatic Dis
December 2024
Department of Urology, St. Elisabeth Hospital Straubing, Brothers of Mercy Hospital, Straubing, Germany.
Background: Despite the relatively low infection rate following transperineal prostate biopsy (TPB), it remains unresolved whether periprocedural antibiotic prophylaxis (PAP) can be omitted. Our aim was to compare infectious complications (genitourinary infections/GUI, fever, sepsis, readmission rate, 30-day-mortality) following TPB, considering all studies of varying levels of evidence that enable a direct comparison between patients with and without PAP.
Methods: We performed a comprehensive search in PubMed/Medline, Embase, Web of Science, and Cochrane databases, as well as grey literature sources, to identify reports published until January 2024.
No impairment of quality of life after radiotherapy for prostate cancer.
Sci Rep
December 2024
Department of Radiation Oncology, University Hospital of Regensburg, Franz-Josef-Strauß Allee 11, Regensburg, Germany.
There are concerns that radiotherapy for prostate cancer influences health-related quality of life in the long term. Furthermore, it is unclear whether postoperative radiotherapy is associated with a different quality of life due to a higher treatment burden compared to patients having received definitive radiotherapy for prostate cancer. This study enrolled 247 patients with localized or locally advanced prostate cancer who received external radiotherapy between 2011 and 2021.
View Article and Find Full Text PDFPhysical activity, fatigue, kinesiophobia and quality of life: comparative study of prostate cancer survivors with healthy controls.
BMJ Support Palliat Care
December 2024
Department of Urology, Necmettin Erbakan University, Meram, Turkey.
Objectives: To determine the distribution of prostate cancer (PCa) patients between physical activity and kinesiophobia, fatigue and quality of life, and to what extent PCa persists compared to healthy males.
Methods: Total of 118 males participated in the study. These participants were allocated into two groups: PCa group (n:59) and control group (n:59).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!