DDR

BRCA-associated pancreatic ductal adenocarcinomas demonstrate recurrent morphologic patterns, including increased glandularity, stromal hyalinization, myxoid stromal change and architectural heterogeneity. These observations provide a framework for future comparative studies investigating morphologic correlates of homologous recombination deficiency in pancreatic cancer. Recognition of these patterns may support consideration of germline or somatic DNA-repair gene testing in appropriate clinical settings.

A single LoF variant in RecQ DNA helicase genes can result in significant DNA repair deficiency, leading to genomic instability and contributing to CRC development in LLS. Therefore, we present evidence for incorporating RECQL5 into genetic testing panels for CRC risk assessment, which would enhance both diagnosis and treatment outcomes.

In this review, we integrate evidence from hepatocellular carcinoma, pancreatic ductal adenocarcinoma, cholangiocarcinoma, colorectal cancer, gastric cancer, esophageal cancer, and gallbladder cancer within a unified framework that links KMT2C domain architecture to enhancer-network destabilization, phenotypic state transitions, and clinical manifestations. We further propose a functional evaluation paradigm that reframes discrete KMT2C variants as graded states of epigenetic deficiency, coupled with a closed-loop validation strategy integrating tissue-based profiling, liquid biopsy monitoring, and spatial multi-omics analyses.

In addition, proanthocyanidins reduced the elevated oxidative stress and recovered the disrupted DNA repair mechanism in the autistic animals by decreasing the expressions of Gadd45a and Parp1 levels and enhancing the expressions of Ogg1, P53, and Xrcc1 genes. This indicates that proanthocyanidins have significant potential as a new therapeutic strategy for alleviating autistic features.

This work establishes a computational framework to build global models integrating all the available clinical parameters and assess their relevance with respect to stiffness, while they are usually explored separately. Similarly, we established spatial statistics techniques to interpolate and model the topographical information embedded in local stiffness maps.

P1/2, N=102, Active, not recruiting, University of Michigan Rogel Cancer Center | Trial completion date: May 2027 --> May 2029 | Trial primary completion date: Nov 2026 --> May 2027

Cell viability profiling across cancer cells shows greater sensitivity to mimosine in cells with DNA repair deficiency. These findings establish the repair pathway dependencies that drive the mechanism of action of mimosine and its use in cancer treatment therapy.

In the DDR-wild-type cohort, independent factors predicting longer OS were IO therapy (compared with each other treatment group: vs. IO+non-IO combinations, p = 0.003; vs. chemotherapy, p < 0.001; vs. anti-DDR agents, p < 0.001; vs. other targeted therapies, p = 0.006), absence of liver metastases (p < 0.001), and normal albumin (p < 0.001) and lactate dehydrogenase (p = 0.001) levels. Prospective studies are warranted to refine the role of DDR alterations as biomarkers of IO response.

The ATR inhibitor also markedly sensitized NBS1 mutants to Etoposide, suggesting that ATR functions as a compensatory pathway in the absence of functional NBS1 during specific types of DNA damage. Collectively, our findings establish valuable NBS1-deficient Chinese hamster cell models that expand understanding of NBS1 function and highlight their utility for investigating DNA repair deficiencies and developing targeted therapeutic approaches for chromosomal instability disorders and cancers with NBS1 mutations.

The CpG-mediated NF-κB activation results in the release of immuno-stimulating cytokines that promote an antitumoral response. As we previously established that G34-mutant DHGs are characterized by DNA repair impairment, we combined CpG dinucleotides with a PARP (poly (ADP-ribose) polymerase) inhibitor, olaparib, in the HDL nanoparticles.

BRCA1-deficient tumors in short survivors have evidence of immunosuppressive c-kit signaling and EMT. Our findings confirm that outcome is not determined by BRCA status alone, but rather a combination of co-occurring genomic alterations, the extent of DNA repair deficiency, and the tumor-immune microenvironment.

In vitro validation using WRN inhibitors demonstrated potent suppression of malignant phenotypes (proliferation, clonogenicity, migration, invasion) in colorectal, endometrial, and ovarian cancer models. Our study suggests that WRN plays a role in cancer diagnosis and therapy, especially in cancers characterized by replicative stress or defective DNA damage repair, and that WRN can serve as a potential target for cancer immunotherapy or targeted therapies and as a prognostic marker for certain tumors.