National Cancer Institute

16S ribosomal RNA modification drives transcript-specific translation efficiency

ABSTRACT Bacterial ribosomal RNAs (rRNAs) are decorated with conserved nucleotide modifications, but the functionality of these modifications is often underexplored. MraW (RsmH) is a 16S rRNA methyltransferase that fine-tunes ribosomal function. We identified a loss-of-function a...

Prediagnostic circulating 25-hydroxyvitamin D and prostate cancer-specific survival: a collaborative pooled analysis of 13 prospective studies

Abstract Background Previous research suggests higher risk of prostate cancer diagnosis in men with high vitamin D serology, but there are limited data related to prostate cancer survival. In this study, we examine the associations between prediagnostic circulating levels of 25-h...

MIR17HG Expression Is Transcriptionally Regulated by PAX3::FOXO1 and MYCN and is Necessary for Oncogenic Activity in Fusion-Positive Rhabdomyosarcoma

Alveolar rhabdomyosarcoma (RMS), an aggressive pediatric soft tissue cancer, is driven by the oncogenic fusion transcription factor PAX3::FOXO1 (P3F) or PAX7::FOXO1. In a subset of fusion-positive (FP)-RMS cases, amplification of the MIR17HG locus leads to overexpression of the m...

Induced proximity-based therapeutics for advanced prostate cancer

Abstract Metastatic castration-resistant prostate cancers (mCRPC) remain dependent on androgen receptor (AR) signaling despite resistance to androgen-deprivation and AR-targeted therapies. Induced proximity-based therapeutics employ event-driven pharmacology to target AR, potenti...

Synergistic lethality of combination treatment with Trop2-directed antibody-drug conjugate sacituzumab govitecan and TRAIL agonists in triple negative breast cancer

Abstract Background Sacituzumab govitecan (SG) is an antibody drug conjugate targeting trophoblast cell surface antigen 2 (Trop2) that is approved for treatment of patients with metastatic triple negative breast cancer (TNBC). Tumor necrosis factor-related apoptosis inducing liga...

Single-cell profiling of peripheral blood mononuclear cells in diverse men with prostate cancer reveals a fatal disease-associated immune signature

Abstract Alterations in peripheral immunity may contribute to fatal prostate cancer and the excessive disease burden among African American (AA) men. Thus, we investigated peripheral immunity in prostate cancer patients in association with disease outcome and AA descent. We perfo...

Portfolio analysis of NCI-funded implementation science grants studying sustainability of cancer control evidence-based practices

Abstract Background Sustainability is a key focus in implementation science given the global challenge of ensuring evidence-based practices (EBPs) deliver long-term benefits across community, public health, and clinical settings. We conducted a portfolio analysis of NCI-funded im...

Targeting Oncogenic KRAS Using Peptide Nucleic Acid Oligomers Attached to Cell-Penetrating Peptides

Approximately 30% of tumors contain an activating mutation in the oncogene KRAS, leading to increased cell proliferation that often promotes non-small cell lung cancers, colorectal adenocarcinomas, pancreatic ductal adenocarcinomas (PDAC), and other cancers. Among the most common...

Top2a complexes with Trim28 to orchestrate stemness of embryonic stem cells and tumorigenesis

Type II topoisomerase α (Top2a) is crucial for maintaining the stemness of embryonic stem cells (ESCs) and is upregulated in various human cancers, yet the mechanisms underlying its cell type-specific functions remain elusive. Here, using an unbiased proteomic approach, we discov...

Autonomous AI in prostate cancer: the road ahead towards clinical implementation

Abstract Artificial Intelligence (AI) for detecting clinically significant prostate cancer (csPCa) on MRI has achieved diagnostic performance comparable to that of radiologists. By autonomously interpreting examinations, AI could improve workflow efficiency and help address incre...

Lipidomic and transcriptomic remodeling underlies early retinal pathogenesis in dry age-related macular degeneration

Abstract Dry age-related macular degeneration (AMD) is initiated by retinal pigment epithelium (RPE) dysfunction, yet early metabolic mechanisms linking RPE injury to photoreceptor dysfunction remain unclear. Using a physiologically relevant mouse model, we performed cell-type–re...

Integrative multiomic analysis identifies transcription factors and target proteins in renal cell carcinoma

Abstract Renal cell carcinoma risk is partly shaped by germline genetic variants that often reside in regulatory regions. However, the transcription factors (TFs) and downstream proteins via which they shape RCC susceptibility remain incompletely characterized. Here we show that...

Therapeutic NAMPT inhibition reveals a targetable metabolic vulnerability in neuroblastoma

Abstract Background Neuroblastoma (NB) remains a major cause of pediatric cancer mortality for which new therapeutic strategies are needed. Exploitation of reprogrammed metabolic pathways offers an opportunity for cell-type specific anticancer therapeutics. To identify pediatric...

The establishment of prostate-specific, SKP2 humanized mice by CRISPR knock-in method reveals neoplastic initiation and microenvironmental reprogramming

Abstract A recent study has shown that SKP2 inactivation can prevent cancer initiation by extension of total cell cycle duration without perturbing normal division, which suggests a new strategy for cancer prevention. However, direct in vivo evidence for human SKP2 on cancer init...