SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

By contrast, sacituzumab govitecan is a TROP-2-targeted ADC conjugated through a hydrolysable CL2A linker to SN-38, the active metabolite of irinotecan. Clinically, trastuzumab deruxtecan has shown substantial efficacy in both HER2-positive and HER2-low breast cancer, whereas sacituzumab govitecan has demonstrated efficacy across triple-negative and hormone receptor-positive/HER2-negative breast cancers. Collectively, these agents highlight how variations in target antigen, linker chemistry, and payload potency impact ADC activity, therapeutic index, and potential strategies for sequential treatment in advanced breast cancer.

These findings suggest that a small subset of non-syndromic PTC cases may carry germline PVs/LPVs in cancer predisposition genes, highlighting the need for broader genetic screening frameworks. Unbiased whole-exome analysis in unselected cohorts can uncover under-recognized genetic risk and guide screening strategies to address the unique hereditary landscape of thyroid cancer in underrepresented populations.

To our knowledge, this first-of-its-kind study highlights the clinical utility of integrating targeted RNA-based NGS into multidisciplinary sarcoma care, enabling diagnostic reclassification in 41.1% of cases most notably in round cell sarcomas with atypical morphology. Both canonical and rare fusions informed individualized therapy, reinforcing RNA-NGS as a pivotal tool for diagnostic refinement and precision oncology in sarcoma management.

These findings suggest a novel role for ZEB1 in promoting ALT both transcriptionally and post-transcriptionally at multiple levels.

Specifically, Sec C initiated MDA-MB-231 cells to yield ROS that induced SLX4 ubiquitination and degradation, leading to mtDNA damage and exacerbated mitophagy and promoted YAP degradation bypassing YAP-driven DNA repair pathways. This study not only demonstrates that Sec C is a rapid and prominent anti-breast cancer drug for TNBC, but also reveals SLX4 as a novel mtDNA stabilizer supporting breast cancer progression, positioning it as both a prognostic biomarker and therapeutic target.

Overall, the histomorphologic, clinical, and molecular features of TFI support its classification as a distinct and benign entity from BCC. In addition, the presence of recurrent SLX4 alterations suggests that TFI are likely not reactive but rather may represent a true neoplasm.

Ginsenoside Rh2 suppresses NF-κB signaling to transcriptionally downregulate FANCL, thereby impairing FA pathway-mediated DNA repair and enhancing cisplatin cytotoxicity in bladder cancer. These findings highlight Rh2 as a potential combinatorial agent to overcome platinum resistance.

We posit that SCAI/REV3 may be required to replicate through and rescue stalled replication forks at fragile genomic regions. Failure to do so leads to increased DNA breakage and genomic instability.

TSN selectively sensitized bladder cancer cells to UVC-induced cytotoxicity (IC50 decreased 35%, P = 0.026, n = 3), without affecting the viability of human urothelial cell SV-HUC-1 cells or lung adenocarcinoma A549 cells (both P > 0.05, n = 3). TSN inhibits FA DNA repair signaling in bladder cancer by suppressing JAK/STAT1-mediated FA core gene transcription, supporting its potential as a combinatorial agent to overcome cisplatin resistance.

The simultaneous functional disruption of both MiDAS and MMEJ pathways upon CIP2A loss provides rationale for the synthetic lethality observed in BRCA1 or 2-deficient cells. These findings position the CIP2A-TOPBP1 axis as a central regulatory hub for mitotic DNA repair, highlighting therapeutic opportunities in tumours characterised by HR deficiency or elevated replication stress.

Our findings uncover piperine as a natural compound that allosterically inhibits UBE2T activity within the FA pathway, thereby impairing ID2 monoubiquitination and enhancing cisplatin sensitivity in bladder cancer. This study highlights the therapeutic potential of piperine and provides a rationale for targeting the FA repair axis to overcome platinum resistance.

One key regulator of nuclease activity is the scaffold protein SLX4, which plays important roles in repairing DNA damage induced by mitomycin C (MMC) and camptothecin (CPT) as well as in the resolution of stalled replication forks...These findings suggest that SLX4 and its associate nucleases are confined within PML NBs and that the optimal protein level of SLX4 is maintained by the coordinated activities of RNF4 and USP7. Our findings provide insight into how cells effectively control the potentially harmful activities of nucleases in the absence of DNA damage by a spatial regulatory mechanism.