Roswell Park Comprehensive Cancer Center

High Expression of Aurora Kinase A (AURKA) is Associated with Aggressive Tumor Biology and Therapeutic Response in ER+/HER2− Breast Cancer

Abstract Background Aurora kinase A ( AURKA ) is a serine/threonine kinase that regulates mitotic entry, spindle assembly, and chromosomal segregation. AURKA overexpression has been linked to multiple malignancies. The biological and clinical significance of AURKA expression with...

Citron kinase activity controls alternative splicing events that drive prostate cancer growth

Prostate cancer (CaP) remains a major cause of cancer death in men, underscoring the need for mechanistically novel therapies. We previously identified the action of the mitotic kinase citron (CIT) kinase as a key driver of CaP progression and promising therapeutic target, but se...

Validation of the International Working Group 2023 response criteria for higher risk myelodysplastic syndromes/neoplasms using the International Consortium for Myelodysplastic Syndromes VALIDATE database and a randomized phase III trial

Response assessment criteria in patients with higher-risk myelodysplastic syndromes/neoplasms (HR-MDS) have been updated in the 2023 International Working Group (IWG) criteria. However, validation of these criteria has been limited to date. We analyzed overall survival (OS) by be...

The chromatin-organizer Satb1 modulates regulatory T cell activity within the tumor microenvironment

Regulatory T cells (Tregs) are essential for maintaining immune homeostasis and preventing autoimmune diseases, but are also a major cellular constituent of the tumor microenvironment (TME) that facilitates cancer progression. Identifying differences in Treg subtypes to specifica...

In Pursuit of Enduring Inactivation: A Perspective on the Development and Study of Irreversible-Covalent Inhibitors

Abstract Molecules that form irreversible covalent bonds with their targets are a mainstay of drug discovery and chemical biology research. Their ability to permanently inactivate an enzyme target provides a mechanism with significant potential to modulate disease phenotypes. Thi...

Targeting Distinct Cell Cycle Nodes Overcomes RAS Inhibitor Resistance

Activating mutations in KRAS drive pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). Although mutant-selective KRAS inhibitors and pan-RAS inhibitors provide clinical benefits, the development of resistance limits durable responses. Here, transcripto...

Smoking‐induced deprivation and subsequent smoking cessation among adults who smoke in four high‐income countries: Trends, correlates and longitudinal associations, 2016–2024

Abstract Background and aims Tobacco smoking substantially contributes to poverty. Smoking‐induced deprivation (SID) occurs when people continue smoking despite financial stress. This study examined (i) trends in SID in Canada, the United States (US), England and Australia from 2...

Tobacco and nicotine product use patterns among young healthcare professionals in Poland: findings from the qualitative component of the NIKO Study

While healthcare professionals (HCPs) are in many ways the best-positioned promoters of smoking cessation, many of them use tobacco and nicotine products (TNPs), which can undermine their credibility. In this paper, we report a qualitative study undertaken to assess TNPs’ use pat...

Obstetric and thrombotic outcomes among pregnant patients with myeloproliferative neoplasms: a propensity score matched real-world analysis

Pregnancies complicated by BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are associated with increased maternal and thrombotic risk; however, large real-world comparative data remain limited. We performed a multicenter retrospective propensity score-matched cohort study...

Development-inspired approach for the derivation of functional and transplantable salivary gland organoids from human pluripotent stem cells

Salivary gland (SG) hypofunction significantly affects the life quality of patients with hyposalivation. Current treatment options for these conditions are limited and often result in undesirable side effects. To address this issue, we’ve developed a developmentally inspired stra...

A Structural Perspective on Non-covalent Targeting of Conserved Polar Residues in Protein Kinases

Abstract All protein kinases contain conserved amino acid residues that bind the ATP substrate molecule and promote catalysis. As an intensely pursued drug target class, kinase inhibitor development is often streamlined by the utilization of three-dimensional structural data and...

Epigenetic Regulation of Sialyltransferase ST6GAL1 Drives Breast Tumor Heterogeneity

Background/Objectives: Tumor progression is often accompanied by sialylation of cell-surface N-glycan glycoproteins with α2-6-linked sialic acids by the sialyltransferase ST6GAL1. Moreover, a hallmark of human cancers is heterogeneity in ST6GAL1 expression among cancer cells, yet...

MACS3: A Peak-calling Platform for Bulk and Single-cell Regulatory Genomics

Since the original publication of Model-based Analysis for ChIP-Seq (MACS), the software has been widely used to identify enriched genomic regions in ChIP-seq, ATAC-seq, CUT&RUN, DNase-seq, and related regulatory genomics assays. Over the years, MACS has evolved substantially, wi...

EPHX2 Loss Promotes CRC Migration via EET ‐Dependent Chemokine Elevation and Mitochondrial Defect

ABSTRACT Epoxide hydrolase 2 (EPHX2) is a key enzyme in fatty acid metabolism that metabolizes epoxyeicosatrienoic acids (EETs), lipid mediators involved in inflammation, angiogenesis, and carcinogenesis. However, the role and mechanism of EPHX2 in colorectal cancer (CRC) migrati...

Hex -MASP for mapping the whole-tissue spatial proteome and the intrabrain distribution of monoclonal antibodies

Abstract Whole-tissue spatial proteomics level provides critical insights into region-specific biological regulations but remains challenging. Previously, we introduced the Micro-scaffold Assisted Spatial Proteomics (MASP) concept for whole-tissue mapping. However, this prototype...

Oxygen-dependent subcellular redistribution of PHD3 links the hypoxic microenvironment to mitochondrial metabolic reprogramming in ccRCC

Abstract Clear cell renal cell carcinoma (ccRCC) is characterized by profound metabolic dysregulation, with both prolyl hydroxylase domain protein 3 (PHD3) and pyruvate carboxylase (PC) independently implicated in disease progression. Although each influences patient outcomes, a...

Repurposing Seleno-L-Methionine as a Pleiotropic Immunomodulatory Agent to Overcome TGF-β1/HIF-Driven Immune Evasion in Clear Cell Renal Cell Carcinoma: Mechanistic Insights and Translational Therapeutic Opportunities

Clear cell renal cell carcinoma (ccRCC) is a highly immune-evasive malignancy that exhibits limited and often transient responses to immune checkpoint inhibitors (ICIs) and remains a major challenge for emerging cellular immunotherapies, including chimeric antigen receptor (CAR)-...

Epidemiology and Species Distribution of Candida Bloodstream Infections in a Comprehensive Cancer Center, 2008–2023

Abstract Introduction Candida bloodstream infections remain a significant complication of malignancies and their therapies. Aim To investigate the epidemiology of Candida species causing bloodstream infections in patients with malignancies. Methods We retrospectively reviewed blo...

Impact of Response to Hypomethylating Agent‐Based Therapy on Survival Outcomes in the Context of Baseline Clinical‐Molecular Risk and Transplant Status in Patients With Higher‐Risk Myelodysplastic Syndromes/Neoplasms: An analysis From the International Consortium for MDS (icMDS)

Baseline IPSS-M risk, response to hypomethylating agent (HMA) therapy, and receipt of allogeneic stem cell transplant (allo-HCT) have all been individually shown to impact overall survival (OS) in patients with myelodysplastic syndromes (MDS). However, the prognostic impact of re...

“I never thought to bring them up to the doctor”: examining symptom appraisal, help-seeking behaviors, and diagnostic delays among young adults with cancer

Abstract Purpose Cancer incidence is rising among young adults (20–39 years), and it is one of the top five causes of death for this age group. Young adults often experience longer delays in diagnosis than children and older adults, which negatively impacts survival and quality o...