TP53 mutation

TROAP aggravated lipid droplet formation and subsequent chemoresistance via de novo lipogenesis via histone acetylation and PI3K/Akt pathway. Aberrant TROAP expression could serve as a biomarker for aggressive behavior and poor prognosis in CRCs, as well as a molecular target for gene therapy.

Given its crucial role in mediating DNA damage responses, we analyzed the p53 protein functionality and downstream target activation in a panel of UM cell lines in response to standard-of-care treatments (i.e., cisplatin and proton-beam irradiation)...Our results indicated a correlation between higher expression levels of Δ40p53α or Δ133p53γ isoforms and the development of more aggressive cancers. Our findings suggest that shorter p53 isoforms can promote cancer aggressiveness and therapy resistance, thereby providing crucial insights into UM pathogenesis.

MTAP is a key biomarker in precision oncology; this work describes the clinical outlook for these patients within the community-oncology setting. These insights can inform future study design, as MTAP-directed therapies continue their development.

Driver alterations in the RAS-MAPK signaling pathway confer radioresistance in metastatic NSCLC. These genetic alterations may serve as biomarkers to personalize RT strategies or as targets to enhance radiosensitivity.

These results suggest that VAF ratios and concurrent mutations can be incorporated into multimodality assessments of pancreatic cysts. Longitudinal studies in patients with a lower initial TP53 VAF ratio are warranted to elucidate whether serial VAF ratios are more accurate markers than a single VAF measurement.

To improve the tolerability of post-transplant maintenance and outcomes despite poor risk disease genetics, we conducted a phase 1 study of venetoclax/FluBu2 RIC transplantation with tacrolimus/methotrexate GVHD prophylaxis followed by all-oral venetoclax/decitabine-cedazuridine (ven/dec-c) maintenance in poor-risk MDS/AML patients (N=30). PROs assessed in first 6-months of maintenance were stable except for emotional function, which improved (P=0.008). Trial is registered at clinicaltrials.gov/NCT03613532.

Additionally, T253I showed a reduction in DNA damage responsive events, diminished DNA binding capabilities, and blunted transactivation capacity. These experimental data lead us to conclude that T253I represents a pathologic variant in TP53 that may predispose to LFS-associated tumors.

Key issues ahead include identifying which genetic features truly affect outcomes, using this information to personalize therapy, predicting who will benefit from targeted drugs, and choosing the best markers to track disease response over time. Looking forward, collaborative efforts are urgently needed to validate pediatric-specific biomarkers, test novel drug combinations, and link genetic data to clinical outcomes to design trials and future treatment strategies.

Notably, MAP2K1 E102-I103 deletion was frequently observed in pre-invasive samples, which endowed alveolar type II cells with increased growth potential and initiated tumor formation, suggesting that it is a potential driver mutation of LUAD. In summary, our study highlights key molecular changes during the stepwise progression of LUAD, provides insights into the identification of novel therapeutic targets, and helps to define the curative time window for this disease.

Our results indicate that integrated morpho-molecular FIGO 2023 staging significantly impacts both stage and risk group stratification, and will benefit EC patients, particularly in high-grade early stage ECs, with potential treatment implications. Further comprehensive studies are needed to fully establish the implications of molecular classification in the FIGO 2023 staging system.

OS was additionally negatively affected when the ten genes were unmutated. Notably, outcomes were excellent for SAR mutations (2-year LFS 76%, OS 84%), indicating allo-HCT in CR1 can overcome their adverse risk at diagnosis.

Trastuzumab-based therapy has shown survival benefit in HER2-positive SEC, leading to its inclusion in current treatment guidelines...The prognostic value remains debated, though recent trials of antibody-drug conjugates (e.g., T-DXd) show promise...Diagnostic challenges include variable scoring systems, intratumoral heterogeneity, and HER2-low classification. Standardization of testing criteria and further clinical validation of HER2-targeted strategies across gynecologic tumors are essential to guide personalized therapy and improve outcomes.