Harnessing STING Signaling and Natural Killer Cells overcomes PARP Inhibitor Resistance in Homologous Recombination Deficient Breast Cancer.

Homologous recombination deficiency (HRD) contributes to genomic instability and leads to sensitivity to poly ADP-ribose polymerase inhibitors (PARPi). HRD also activates the cyclic GMP-AMP synthase (cGAS)-STimulator of INterferon Genes (STING)-Interferon (IFN) pathway, highlighting the need to understand the impact of cGAS-STING-IFN signaling on PARPi efficacy. In this study, we analyzed a cohort of thirty-five breast cancer (BC) patient-derived xenografts (PDX) and mouse-derived allografts (MDA).

DNA Methylation Dynamics and Prognostic Implications in Metastatic Differentiated Thyroid Cancer.

Distant metastases (DM) are the leading cause of thyroid cancer-related death in patients with differentiated thyroid cancer (DTC). Despite significant progress in understanding DNA methylation in DTC, the methylation landscape of metastatic primary tumors and DM remains unclear. Our primary objective was to investigate DNA methylation dynamics during DTC progression, with a secondary goal of assessing potential clinical implications.

Exposomal determinants of non-genetic plasticity in tumor initiation.

The classical view of cancer as a genetically driven disease has been challenged by recent findings of oncogenic mutations in phenotypically healthy tissues, refocusing attention on non-genetic mechanisms of tumor initiation. In this context, gene-environment interactions take the stage, with recent studies showing how they unleash and redirect cellular and tissue plasticity towards protumorigenic states in response to the exposome, the ensemble of environmental factors impinging on tissue homeostasis. We conceptualize tumor-initiating plasticity as a phenotype-transforming force acting at three levels: cell-intrinsic, focusing on mutant epithelial cells' responses to environmental variation; reprogramming of non-neoplastic cells of the host, leading to protumor micro- and macroenvironments; and microbiome ecosystem dynamics.

Multimodal data integration in early-stage breast cancer.

The use of biomarkers in breast cancer has significantly improved patient outcomes through targeted therapies, such as hormone therapy anti-Her2 therapy and CDK4/6 or PARP inhibitors. However, existing knowledge does not fully encompass the diverse nature of breast cancer, particularly in triple-negative tumors. The integration of multi-omics and multimodal data has the potential to provide new insights into biological processes, to improve breast cancer patient stratification, enhance prognosis and response prediction, and identify new biomarkers.

Red Deer Resequencing Reveals the Importance of Sex Chromosomes for Reconstructing Late Quaternary Events.

Sex chromosomes differ in their inheritance properties from autosomes and hence may encode complementary information about past demographic events. We compiled and analyzed a range-wide resequencing data set of the red deer (Cervus elaphus), one of the few Eurasian herbivores of the Late Pleistocene megafauna still found throughout much of its historic range. Our analyses of 144 whole genomes reveal striking discrepancies between the population clusters suggested by autosomal and X-chromosomal data.