‘Where is my gap’: mechanisms underpinning PARP inhibitor sensitivity in cancer

Biochemical Society Transactions, Год журнала: 2025, Номер 53(01)

Опубликована: Фев. 10, 2025

The introduction of poly-ADP ribose polymerase (PARP) inhibitors (PARPi) has completely changed the treatment landscape breast cancer susceptibility 1–2 (BRCA1–BRCA2)-mutant cancers and generated a new avenue research in fields DNA damage response therapy. Despite this, primary secondary resistances to PARPi have become challenge clinic, novel therapies are urgently needed address this problem. After two decades research, unifying model explaining sensitivity cells is still missing. Here, we review current knowledge field increasing evidence pointing crucial role for replicative gaps mediating sensitization BRCA-mutant ‘wild-type’ cells. Finally, discuss challenges be addressed further improve utilization tackle emergence resistance clinical context.

Язык: Английский

Characterizing the Ovarian Cytogenetic Dynamics of Sichuan Bream (Sinibrama taeniatus) During Vitellogenesis at a Single-Cell Resolution

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 2265 - 2265

Опубликована: Март 4, 2025

Vitellogenesis in fish represents a critical phase of oogenesis, significantly influencing the nutritional provisioning for oocyte maturation and subsequent offspring development. However, research on physiological mechanisms governing vitellogenesis at single-cell level remains limited. In this study, we performed single-nucleus RNA sequencing (snRNA-seq) ovaries Sichuan bream (Sinibrama taeniatus). We first identified six distinct cell types (germ cells, follicular immune stromal endothelial epithelial cells) based typical functional marker genes. Subsequently, reconstructed developmental trajectory germ cells using pseudotime analysis, which describes transcriptional dynamics various stages. Additionally, transcription factors (TFs) specific to that exhibit high activity each stage. Furthermore, analyzed genetic heterogeneity different stages elucidate their contributions vitellogenesis. Finally, interaction analysis revealed communicate with somatic or other via multiple receptors ligands regulate growth, development, yolk acquisition. These findings enhance our understanding underlying fish, providing theoretical foundation regulating ovarian development farmed fish.

Язык: Английский