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Androgen receptor inhibition increases MHC Class I expression and improves immune response in prostate cancer.
Cancer Discov
December 2024
Oregon Health & Science University, Portland, OR, United States.
Tumors escape immune detection and elimination through a variety of mechanisms. Here, we used prostate cancer as a model to examine how androgen-dependent tumors undergo immune evasion through downregulation of the major histocompatibility complex class I (MHCI). We report that response to immunotherapy in late-stage prostate cancer is associated with elevated MHC expression.
View Article and Find Full Text PDFLow tristetraprolin expression activates phenotypic plasticity and primes transition to lethal prostate cancer in mice.
J Clin Invest
November 2024
Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Article Synopsis
- - Phenotypic plasticity in cancer, particularly prostate cancer (PCa), leads to resistance against androgen receptor-targeted therapies, highlighting the need to understand its driving mechanisms to prevent resistance emergence.
- - The study found that loss of the tristetraprolin (TTP) gene (ZFP36) increases NF-κB activation, correlating with more aggressive disease and recurrence, especially when PTEN, another key driver in PCa, is also lost.
- - Targeting the NF-κB pathway with an inhibitor (DMAPT) showed promising therapeutic effects in tumors exhibiting co-loss of ZFP36 and PTEN, suggesting a potential new treatment strategy for castration-resistant PCa.
Pre-operative stereotactic radiosurgery and peri-operative dexamethasone for resectable brain metastases: a two-arm pilot study evaluating clinical outcomes and immunological correlates.
Nat Commun
October 2024
Department of Radiation Oncology, Emory University, Atlanta, USA.
Enhancing the efficacy of immunotherapy in brain metastases (BrM) requires an improved understanding of the immune composition of BrM and how this is affected by radiation and dexamethasone. Our two-arm pilot study (NCT04895592) allocated 26 patients with BrM to either low (Arm A) or high (Arm B) dose peri-operative dexamethasone followed by pre-operative stereotactic radiosurgery (pSRS) and resection (n= 13 per arm). The primary endpoint, a safety analysis at 4 months, was met.
View Article and Find Full Text PDFA deep-learning framework to predict cancer treatment response from histopathology images through imputed transcriptomics.
Nat Cancer
September 2024
Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Advances in artificial intelligence have paved the way for leveraging hematoxylin and eosin-stained tumor slides for precision oncology. We present ENLIGHT-DeepPT, an indirect two-step approach consisting of (1) DeepPT, a deep-learning framework that predicts genome-wide tumor mRNA expression from slides, and (2) ENLIGHT, which predicts response to targeted and immune therapies from the inferred expression values. We show that DeepPT successfully predicts transcriptomics in all 16 The Cancer Genome Atlas cohorts tested and generalizes well to two independent datasets.
View Article and Find Full Text PDFLocalized high-risk prostate cancer harbors an androgen receptor low subpopulation susceptible to HER2 inhibition.
medRxiv
February 2024
Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Patients diagnosed with localized high-risk prostate cancer have higher rates of recurrence, and the introduction of neoadjuvant intensive hormonal therapies seeks to treat occult micrometastatic disease by their addition to definitive treatment. Sufficient profiling of baseline disease has remained a challenge in enabling the in-depth assessment of phenotypes associated with exceptional vs. poor pathologic responses after treatment.
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