Prostate cancer (PCa) is one of the most commonly diagnosed malignancies and among the leading causes of cancer-related death worldwide. It is a highly heterogeneous disease, ranging from remarkably slow progression or inertia to highly aggressive and fatal disease. As therapeutic decision-making, clinical trial design and outcome highly depend on the appropriate stratification of patients to risk groups, it is imperative to differentiate between benign versus more aggressive states. The incorporation of clinically valuable prognostic and predictive biomarkers is also potentially amenable in this process, in the timely prevention of metastatic disease and in the decision for therapy selection. This review summarizes the progress that has so far been made in the identification of the genomic events that can be used for the classification, prediction and prognostication of PCa, and as major targets for clinical intervention. We include an extensive list of emerging biomarkers for which there is enough preclinical evidence to suggest that they may constitute crucial targets for achieving significant advances in the management of the disease. Finally, we highlight the main challenges that are associated with the identification of clinically significant PCa biomarkers and recommend possible ways to overcome such limitations.
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http://dx.doi.org/10.1016/j.pharmthera.2021.107932 | DOI Listing |
Prostate Cancer Prostatic Dis
January 2025
Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Introduction: Androgen deprivation therapy intensification (ADTi) with androgen receptor pathway inhibitors (ARPI), docetaxel or both has been shown to improve survival outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Currently, baseline tumor genomic markers have no role in clinical decision-making in patients with mHSPC.
Methods: In this IRB-approved retrospective study, patients diagnosed with mHSPC who underwent comprehensive genomic profiling from primary tissue or metastatic sites and treated with ADTi were included.
Br J Cancer
January 2025
School of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK.
Background: Prostate cancer (PC) is the commonest male visceral cancer, and second leading cause of cancer mortality in men in the Western world.
Methods: Using a forward-mutagenesis Sleeping Beauty (SB) transposon-based screen in a Probasin Cre-Recombinase (Pb-Cre) Pten-deficient mouse model of PC, we identified Arid1a loss as a driver in the development of metastatic disease.
Results: The insertion of transposon in the Arid1a gene resulted in a 60% reduction of Arid1a expression, and reduced tumour free survival (SB:Pten Arid1a median 226 days vs SB:Pten Arid1a 293 days, p = 0.
Sci Rep
January 2025
Jun Shi Department of Ultrasound, The First Hospital of Hebei Medical University, Shijiazhuang City, 050031, Hebei Province, China.
Transrectal shear wave elastography (T-SWE) can be used non-invasively to diagnose prostate cancer (PCa) and benign prostatic hyperplasia (BPH). The prostate tissue can be viewed as an ellipsoidal sphere with viscoelastic characterization. Linear elastic model has been used to characterize soft tissues, and the simplification of partial characterization provides incomplete information.
View Article and Find Full Text PDFNat Commun
January 2025
Klinik für Urologie und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Freiburg, Germany.
Prostate cancer (PCa) growth depends on de novo lipogenesis controlled by the mitochondrial pyruvate dehydrogenase complex (PDC). In this study, we identify lysine methyltransferase (KMT)9 as a regulator of PDC activity. KMT9 is localized in mitochondria of PCa cells, but not in mitochondria of other tumor cell types.
View Article and Find Full Text PDFEur Urol
January 2025
South Australian Immunogenomics Cancer Institute, University of Adelaide Adelaide Australia. Electronic address:
Background And Objective: In the phase 3 IPATential150 trial, ipatasertib addition to abiraterone significantly reduced the risk of disease progression in men with metastatic castration-resistant prostate cancer (mCRPC) with PTEN loss on immunohistochemistry (IHC), but not in the intention-to-treat (ITT) population. Here we report the final overall survival (OS) analysis and present results for prespecified and exploratory biomarker analyses.
Methods: Patients were randomized to receive ipatasertib (400 mg once daily) or placebo.
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