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Randomized controlled trials (RCTs) evaluating anti-cancer agents often lack generalizability to real-world oncology patients. Although restrictive eligibility criteria contribute to this issue, the role of selection bias related to prognostic risk remains unclear. In this study, we developed TrialTranslator, a framework designed to systematically evaluate the generalizability of RCTs for oncology therapies.
View Article and Find Full Text PDFTumor-intrinsic regulators of the immune-cold microenvironment of prostate cancer.
Trends Endocrinol Metab
January 2025
Department of Urology, Emory University School of Medicine, Atlanta, GA, USA; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA. Electronic address:
Prostate cancer (PC) is a notoriously immune-cold tumor in that it often lacks substantial infiltration by antitumor immune cells, and in advanced diseases such as neuroendocrine PC, it could be devoid of immune cells. A majority of PC patients thus have, unfortunately, been unable to benefit from recent advances in immunotherapies. What causes this immunosuppressive microenvironment around PC? In this review, we discuss various genetic and epigenetic regulators intrinsic to prostate tumor cells that could have profound effects on the tumor microenvironment, thus contributing to this immune-cold status.
View Article and Find Full Text PDFClonal phylogenies inferred from bulk, single cell, and spatial transcriptomic analysis of epithelial cancers.
PLoS One
January 2025
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
Epithelial cancers are typically heterogeneous with primary prostate cancer being a typical example of histological and genomic variation. Prior studies of primary prostate cancer tumour genetics revealed extensive inter and intra-patient genomic tumour heterogeneity. Recent advances in machine learning have enabled the inference of ground-truth genomic single-nucleotide and copy number variant status from transcript data.
View Article and Find Full Text PDFSystems-level liquid biopsy in advanced prostate cancer.
Endocr Relat Cancer
January 2025
S Dehm, Masonic Cancer Center, University of Minnesota, Minneapolis, United States.
Treatment for castration-resistant prostate cancer (CRPC) primarily involves the suppression of androgen receptor (AR) activity using androgen receptor signaling inhibitors (ARSIs). While ARSIs have extended patient survival, resistance inevitably develops. Mechanisms of resistance include genomic aberrations at the AR locus that reactivate AR signaling, or lineage plasticity that drives emergence of AR-independent phenotypes.
View Article and Find Full Text PDFNeoadjuvant darolutamide plus androgen deprivation therapy for high-risk and locally advanced prostate cancer: a multicenter, open-label, single-arm, phase II trial.
World J Urol
January 2025
Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Propose: This study aimed to evaluate the efficacy and safety of neoadjuvant treatment of darolutamide, a next-generation androgen receptor inhibitor, plus androgen deprivation therapy (ADT) for patients with locally advanced prostate cancer (LAPC).
Methods: This single-arm, multicenter, open-label phase II trial (ClinicalTrials.gov: NCT05249712, 2022-01-01), recruited 30 localized high-risk/very high-risk prostate cancer (HRPCa/VHRPCa) patients from three centers in China between 2021 and 2023.
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