DDR

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.

BPA-BNCT exerts potent and selective antitumor effects against cervical cancer through a dual mechanism: LAT1-mediated boron delivery ensures tumor specificity, while the resulting high-linear energy transfer radiation induces DNA damage that capitalizes on the inherent limitations of the tumor cells' DNA repair capacity, leading to catastrophic cell death. The therapy demonstrates a distinct advantage in treating adenocarcinoma subtypes, which are typically less responsive to conventional radiotherapy. These findings provide robust preclinical evidence supporting BNCT as a promising therapeutic approach, particularly for radiotherapy-resistant cervical adenocarcinoma.

Using publicly available panel sequencing data, we find that ERCC2 wild type (WT) bladder cancer cases that have high levels of this mutational signature respond better to neoadjuvant platinum therapy and have improved overall survival compared to ERCC2 WT cases with low levels of the signature. We also find that other solid tumor types with ERCC2 mutations also show the characteristic mutational signature seen in NER-deficient ERCC2 -mutant bladder cancers, suggesting a novel approach to therapeutically target these ERCC2 -mutant solid tumors beyond bladder cancer.

Tumor profiling also uncovers actionable mutations in oncogenes like RET and VHL, which can be targeted with specific therapies. This review explores the integration of tumor molecular features with germline genetic data to refine diagnosis, risk assessment, and therapeutic strategies in hereditary cancer.