ATM (ATM serine/threonine kinase)

P2, N=88, Active, not recruiting, University of Maryland, Baltimore | Recruiting --> Active, not recruiting

Viral infection induced an overexpression of DDR genes, suggesting a role of the virus in manipulating DDR to favor its replication or contribute to tumor progression. These preliminary results provide in vitro models for studying the interplay between MCPyV and DDR within malignant and non-malignant contexts across the respiratory tract, laying the basis for future research exploring the clinical relevance of DDR activation in virus-driven malignancies.

P2, N=140, Recruiting, Andrea DeCensi | N=95 --> 140

These findings confirm ATM as a clinically relevant BC susceptibility gene in North Macedonia and highlight the population-specific enrichment of both PVs and the p.(Leu2492Arg) missense variant. The results emphasize the importance of using population-matched controls and regional genomic data for accurate risk assessment and variant interpretation.

In ATM-deficient cancer cells, cGAS dictates replication stress and ATR inhibitor sensitivity, highlighting its potential as a biomarker for ATR-targeted therapy. Together, our findings uncover a regulatory circuit in which ATM and chromatin-bound cGAS jointly maintain the homeostasis of replication and cGAS signalling in cycling cells.

Our findings will help in the clinical management of families where an ATM PV/PPV segregates.

However, uncertainties remain regarding the magnitude of benefit, eligibility criteria, surveillance start age, cost-effectiveness, and the risk of overdiagnosis. This review critically appraises current evidence, focusing on the Italian and European experience, evaluates the pros and cons of HRIs surveillance, and proposes updated criteria and considerations for a structured, registry-based national program aligned with new evidence.

We examine how these approaches can be leveraged to improve standard chemotherapeutic and immunotherapeutic treatments in cancer. Additionally, we highlight the key preclinical and clinical studies evaluating ATM as a predictive biomarker and discuss its evolving role in precision oncology.

P2, N=83, Active, not recruiting, Rahul Aggarwal | Recruiting --> Active, not recruiting

Longitudinal cfDNA WES captured dynamic clonal remodeling under immunotherapy and anticipated radiological outcomes. These findings underscore the clinical necessity of integrating dynamic molecular monitoring by liquid biopsy to overcome the limitations of static PD-L1 assessment, refine therapeutic stratification, and identify early resistance mechanisms in advanced NSCLC.

Thus, by integrating protein language models with experimentally validated functional data, our approach enables accurate, interpretable VEP for TP53, overcoming limitations of predictors trained solely on evolutionary or clinical associations. We further extended this framework to five additional cancer-related genes (VHL, ATM, BRCA1, RAD51C, and BAP1), establishing a generalizable framework for gene-specific VEP with potential applications in precision medicine.

P2, N=140, Not yet recruiting, Dana-Farber Cancer Institute