PPARγ acetylation governs mammary adenocarcinoma tumor growth via acetylated residues that determine DNA sequence-specific binding.

Peroxisome proliferator-activated receptor γ (PPARγ), which is expressed in a variety of malignancies, governs biological functions through transcriptional programs. Defining the molecular mechanisms governing the selection of canonical versus non-canonical PPARγ binding sequences may provide the opportunity to design regulators with distinct functions and side effects. Acetylation at K268/293 in mouse Pparγ2 participates in the regulation of adipose tissue differentiation, and the conserved lysine residues (K154/155) in mouse Pparγ1 governs lipogenesis in breast cancer cells.

Identification of Deregulated Proteins in Mutated / Breast and Ovarian Cancers for Vectorized Biologics.

Administration of PARP inhibitors against breast and ovarian cancers with BRCA1 and BRCA2 mutations has shown clinical benefits in patients. However, these agents are also toxic and have a narrow therapeutic index. In this work, we aimed to identify membrane proteins that are specifically upregulated in these cancers.

PCSK9 expression and cancer survival: a prognostic biomarker at the intersection of oncology and geroscience.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily recognized for its role in cholesterol metabolism; however, emerging evidence suggests it plays a broader role in the regulation of cellular aging mechanisms and the pathogenesis of age-related diseases. Given that cancer is an age-related disease, PCSK9 has garnered attention for its potential impact on tumor progression and patient survival. In this study, we conducted a comprehensive analysis of PCSK9 expression across multiple tumor types, assessing its prognostic significance using RNA sequencing data from The Cancer Genome Atlas (TCGA) and gene expression microarray data from the Gene Expression Omnibus (GEO).

The Prognostic Value of the Hedgehog Signaling Pathway in Ovarian Cancer.

The hedgehog pathway is a major regulator of cell growth and differentiation during embryogenesis and early development. The literature suggests that variations in this pathway's genes play a role in tumor progression and response to therapy. This study aimed to assess the correlation between the expression levels of selected genes of this pathway and the progression-free and overall survival of ovarian cancer patients.

Truncated DAPK Variants Restore Tumor Suppressor Activity and Synergize with Standard Therapies in High-Grade Serous Ovarian Cancer.

Background/objectives: Death-associated protein kinase 1 (DAPK1) is a serine/threonine kinase that plays a crucial role in cancer by regulating apoptosis through interactions with TP53. Aberrant expression of DAPK1 was shown in certain types of human cancer contributing to tumor progression and chemoresistance. This study aimed to investigate the role of DAPK1 in high-grade serous ovarian cancer (HGSOC) and to evaluate the therapeutic potential of restoring its kinase activity, including the use of truncated DAPK1 variants, to overcome chemoresistance and enhance tumor suppression.

Exploring immune activation patterns in HER2-low and HER2-ultralow breast cancer subtypes.

Background: A deeper understanding of the molecular and clinical characteristics of HER2-low and ultralow breast cancer (BC) subtypes is essential for advancing therapeutic strategies.

Methods: Three independent GEO datasets with microarray and IHC/FISH data from 510 BC patients were analyzed to establish reliable HER2 expression cutoff values (>3034 for HER2-positivity and <1780 for HER2-ultralow), defining HER2-positive (HER2+), HER2-low, and HER2-ultralow cohorts. Combined with hormone receptor status, six distinct BC subgroups were identified.

CTHRC1 promotes bone metastasis in prostate cancer.

Prostate cancer causes a high frequency of bone metastases. The purpose of this study was to identify molecules that regulate prostate cancer bone metastasis as potential therapeutic and/or prognostic targets in prostate cancer, using integrative genome-wide data. Based on the biological characterization of prostate cancer cell lines and integrated big data analysis of clinical samples, we identified CTHRC1 as a candidate gene that regulates prostate cancer bone metastasis.

NRF2 pathway activation predicts poor prognosis in lung cancer: a cautionary note on antioxidant interventions.

Lung cancer is a leading cause of cancer-related mortality worldwide. As an age-related disease, its pathogenesis is shaped by several molecular hallmarks of aging, including impaired DNA repair and diminished stress resilience. The transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) is a master regulator of oxidative stress defense and cellular survival.

A gene set enrichment analysis for cancer hallmarks.

The "hallmarks of cancer" concept provides a valuable framework for understanding fundamental organizing principles common to various cancers. However, without a consensus gene set for cancer hallmarks, data comparison and integration result in diverse biological interpretations across studies. Therefore, we aimed to form a consensus cancer hallmark gene set by merging data from available mapping resources and establishing a framework for mining these gene sets.

Quantifying the impact of treatment delays on breast cancer survival outcomes: a comprehensive meta-analysis.

Treatment delay in breast cancer care represents a significant concern in oncology, potentially impacting patient survival outcomes. While various factors can contribute to delayed treatment initiation, the quantitative relationship between specific delay intervals and survival remains incompletely understood in breast cancer management. Our study aims to explore the impact of treatment delays on survival outcomes in breast cancer.

Adipocyte/Tumor cell crosstalk via IGF-1/TXNIP axis promotes malignancy and endocrine resistance in breast cancer.

Background: Despite significant improvements in the outcome of Estrogen Receptor (ER) α-positive breast cancer (BC) following the use of endocrine therapies, resistance remains a major challenge. Clinical studies proved that obesity, in addition to promote BC progression, is associated with a reduced efficacy to these treatments, but mechanisms remain unclear.

Methods: We used co-culture systems followed by validation through an ‘ex vivo’ model of human mammary obese (Ob) adipocytes and obese endocrine-resistant metastatic Patient-Derived Organoids (PDOs).

Quantum Size Effects on Andreev Transport in Nb/Au/Nb Josephson Junctions: A Combined Ab Initio and Experimental Study.

We have measured the critical current density, superconducting coherence length, and superconducting transition temperature of single-domain, epitaxially grown Nb(110)/Au(111)/Nb(110) trilayers, all of which show a nonmonotonic dependence on the thickness of the Au layer. These results are compared with the predictions of a relativistic, ab initio theory, which incorporates superconducting correlations. We find good agreement with experiment, coming from a rich interplay between superconducting proximity and quantum size effects, mediated by Andreev bound states.

In silico evaluation of the immunogenic profile of lung cancers with SMARCA4 genetic alterations.

Genomic alterations in tumor cells can influence immune response, as has been demonstrated in several tumor types. For instance, mutations in certain genes like EGFR or B-RAF are associated with a particular immune phenotype. Non-small cell lung cancer (NSCLC) is one of the most immunogenic tumors, but certain genomic alterations can modulate and influence immune response.

No detectable impact of short-term treatment delays on lung cancer survival.

Timely initiation of treatment is a core principle of oncologic care, especially for aggressive cancers such as lung cancer. However, the real-world impact of short-term delays in treatment initiation on survival outcomes in lung cancer remains unclear. This meta-analysis evaluates the association between treatment delays of 4, 8, and 12 weeks and all-cause mortality in lung cancer patients.

Unlocking the power of immune checkpoint inhibitors: Targeting YAP1 reduces anti-PD1 resistance in skin cutaneous melanoma.

Background And Purpose: Immune checkpoint inhibitors, such as anti-PD1, revolutionized melanoma treatment. However, resistance and low response rates remain problems. Our goal was to pinpoint actionable biomarkers of resistance to anti-PD1 treatment and verify therapeutic effectiveness in vivo.

Melanoma Proteomics Unveiled: Harmonizing Diverse Data Sets for Biomarker Discovery and Clinical Insights via MEL-PLOT.

Using several melanoma proteomics data sets we created a single analysis platform that enables the discovery, knowledge build, and validation of diagnostic, predictive, and prognostic biomarkers at the protein level. Quantitative mass-spectrometry-based proteomic data was obtained from five independent cohorts, including 489 tissue samples from 394 patients with accompanying clinical metadata. We established an interactive R-based web platform that enables the comparison of protein levels across diverse cohorts, and supports correlation analysis between proteins and clinical metadata including survival outcomes.

Depression increases cancer mortality by 23-83%: a meta-analysis of 65 studies across five major cancer types.

Depression is a prevalent but often underrecognized comorbidity among cancer patients. Emerging evidence suggests that psychological distress may adversely impact cancer outcomes, but the magnitude of its effect on survival remains unclear. This meta-analysis evaluates the association between depression diagnosed after cancer diagnosis and cancer-specific and all-cause mortality across major cancer types.

Exercise and survival benefit in cancer patients: evidence from a comprehensive meta-analysis.

Cancer remains a major global health challenge, and growing evidence suggests that physical activity is a key modifiable factor that may improve survival outcomes in cancer patients. However, a comprehensive, large-scale synthesis of the effects of post-diagnosis physical activity across multiple cancer types remains lacking. This meta-analysis aims to systematically evaluate the association between physical activity and survival in patients diagnosed with breast, lung, prostate, colorectal, and skin cancers.

Sleep disorders increase the risk of dementia, Alzheimer's disease, and cognitive decline: a meta-analysis.

Sleep disorders, particularly insomnia and obstructive sleep apnea, are increasingly implicated as significant contributors to cognitive decline, dementia, and neurodegenerative diseases such as Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID). However, the extent and specificity of these associations remain uncertain. This meta-analysis evaluates the impact of common sleep disorders on the risk of developing dementia and cognitive decline.

Association between red and processed meat consumption and colorectal cancer risk: a comprehensive meta-analysis of prospective studies.

Increasing evidence suggests that red and processed meat consumption may elevate the risk of colorectal cancer (CRC), yet the magnitude and consistency of this association remain debated. This meta-analysis aims to quantify the relationship between red and processed meat intake and the risk of CRC, colon cancer, and rectal cancer using the most comprehensive set of prospective studies to date. We conducted a comprehensive search in PubMed, Web of Science, Cochrane Library, Embase, and Google Scholar databases from 1990 to November 2024, to identify relevant prospective studies examining red, processed, and total meat consumption in relation to colorectal, colon, and rectal cancer risk.

Treatment delay significantly increases mortality in colorectal cancer: a meta-analysis.

Delaying the initiation of cancer treatment increases the risk of mortality, particularly in colorectal cancer (CRC), which is among the most common and deadliest malignancies. This study aims to explore the impact of treatment delays on mortality in CRC. A systematic literature search was conducted in PubMed, Web of Science, and Scopus for studies published between 2000 and 2025.

Prognostic impact of a senescence gene signature in multiple myeloma.

Multiple myeloma (MM), an incurable malignancy of plasma cells, is predominantly an age-related disease, with the majority of cases occurring in patients over the age of 60. Cellular senescence, a fundamental biological process underlying aging, has been increasingly recognized for its critical role in developing age-related malignancies. In this study, we aimed to investigate the prognostic significance of genes implicated in the molecular mechanisms of senescence within a large cohort of MM patients.

Integrating artificial intelligence in drug discovery and early drug development: a transformative approach.

Artificial intelligence (AI) can transform drug discovery and early drug development by addressing inefficiencies in traditional methods, which often face high costs, long timelines, and low success rates. In this review we provide an overview of how to integrate AI to the current drug discovery and development process, as it can enhance activities like target identification, drug discovery, and early clinical development. Through multiomics data analysis and network-based approaches, AI can help to identify novel oncogenic vulnerabilities and key therapeutic targets.