National Cancer Institute

High-grade astrocytoma with piloid features: a clinical and genomic analysis of prognostic factors using a large cohort

BACKGROUND: High-grade astrocytoma with piloid features (HGAP) is a recently defined tumor type that is not well-understood. Prognostic factors of clinical outcomes are not well-established. METHODS: Methylation profiling was performed on tumor samples, many at the National Cance...

Why Women Don't Return: Nurse Perspectives on Follow‐Up Care After Abnormal Cervical Cancer Screening Results in Mississippi's Public Health System

ABSTRACT Objective To explore public health nurses’ perspectives on reasons women in Mississippi may fail to receive follow‐up care after abnormal cervical cancer (CC) screenings. Background Mississippi’s high cervical cancer mortality rate poses a significant public health chall...

Oral Fungal Infection Impacts Epithelial Innate Immunity to Promote Local and Distal Squamous Cell Carcinoma Progression

Abstract Fungi have been detected within human tumors and shown to support tumor progression. A better understanding of how intratumoral fungi evade innate immunity, remodel the tumor microenvironment (TME), and promote tumorigenesis may provide insights into cancer pathogenesis...

TMA-Grid: an open-source, zero-footprint web application for FAIR tissue microarray de-arraying

Tissue microarrays (TMAs) significantly increase analytical efficiency in histopathology and large-scale epidemiologic studies by allowing multiple tissue cores to be scanned on a single slide. The individual cores can be digitally extracted and then linked to metadata for analys...

Adaptation and Usability of a Lifestyle Cancer Prevention Screener for US Populations: A Mixed Methods Study

Abstract Background: The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations provide evidence-based guidance on modifiable lifestyle factors associated with cancer risk. While a standardized scoring system exists to asse...

Associations between a mixture of trace elements and bladder cancer occurrence

Background: The association between trace elements and bladder cancer risk is not well understood. Individuals are typically exposed to a mixture of multiple elements simultaneously, such as through water pollution or diet. While previous studies have explored associations betwee...

Transcriptome-based synthetic lethality predictions to improve targeted therapy/immunotherapy treatment prioritization in non-metastatic breast cancer: BC-SELECT

Abstract Patients with non-metastatic triple-negative (TNBC) or HER2-positive (HER2+) breast cancer do not have tools to predict treatment response or prioritize options prior to starting therapy. Pathologic complete response (pCR) is a proxy that requires neoadjuvant treatment....

Phosphorylation Protects Oncogenic RAS from LZTR1-Mediated Degradation

Oncogenic KRAS and NRAS mutations are common in hematologic malignancies, but how they signal is less well characterized than in carcinomas. To uncover novel RAS biology and potential therapeutic vulnerabilities, we employed a multi-omics screening approach in multiple myeloma to...

Overcoming immune checkpoint inhibitor-mediated T-cell exhaustion with a TCR β chain-directed selective dual T-cell activator

Abstract Background Resistance to immune checkpoint inhibition (ICI) using antibodies against the PD-1/PD-L1 axis remains a significant clinical challenge. Here, we report that combination of anti-PD-1 with a bifunctional fusion molecule, anti-TCRβ-IL-2, comprised of a monovalent...

MUTYH Activity Maintains Telomere Stability in Response to Chronic Telomeric 8-Oxoguanine Damage in Cancer Cells

Telomeres are highly susceptible to oxidative DNA damage, particularly 8-oxoguanine (8-oxoG), which is processed by glycosylase-initiated base excision repair (BER). OGG1 removes 8-oxoG opposite C, and MUTYH removes A misinserted opposite 8-oxoG to prevent mutations. While OGG1 h...

Spindle Assembly Checkpoint Competency Determines Sensitivity to KIF18A Inhibition in Small-Cell Lung Cancer

Background: Small-cell lung cancer (SCLC) is characterized by pervasive chromosomal instability (CIN) and remains largely refractory to targeted therapies. KIF18A, a motor protein that regulates chromosome alignment during mitosis, has emerged as a selective dependency in CIN-hig...

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...

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...

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...

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...

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...

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...