TP53 wild-type

Consistently, supplementing primary HER2-positive tumor cultures with recombinant SAA1, SAA2, or THBS4 peptides enhanced tumor cell proliferation and migration. Together, these findings uncover a mechanism by which fibroblastic mutant p53 promotes mammary tumorigenesis-through upregulating secretory proteins such as SAA1, SAA2, and THBS4 in the stroma, thereby enhancing PI3K/AKT signaling and tumor progression.

In mutant p53 cells, combination therapy may provide partial benefits. These findings support ALRN-6924 clinical development as targeted therapy for p53-functional CLL, particularly in combination strategies.

The FIGO 2023 stage IA3 classification enables more precise risk stratification, particularly, in cases with low-grade tumors, estrogen receptor positivity, and favorable molecular profiles (POLE-mutated or p53 wild-type and non-specific molecular profile). However, it raises 2 critical issues: the need for appropriate staging surgery and the debate regarding the optimal grading system for ovarian endometrioid carcinoma.

Lastly, EBVaGC is more likely to express the PI3K and ARID1A mutations, which can potentially be treated using PI3K/mTOR dual inhibitors and Akt/PARP inhibitors. These six subtypes could aid the selection of more successful treatments for EBVaGC, thereby improving the current overall survival and prognosis of patients.

In addition, Nutlin-3 treatment decreased the EDmax value in p53 wild-type U2OS cells from 0.43 to 0.20. In summary, our method can identify p53-MDM2 interaction inhibitors in living cells, providing a quantitative in vivo supplement for traditional target-based drug discovery.

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.

High doses of idasanutlin decreased the proliferation of T cells and depleted T cell numbers within the lymphocyte population, as we show in vitro and in vivo. These findings suggest that low doses of MDM2 antagonists may enhance immunotherapy, while higher doses could interfere with immunotherapy by p53-mediated cell cycle arrest and decreasing the proliferation of the immune cells.

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.

Patients ≥60 years with Ph-negative B-cell ALL and TP53 VAF ≥45% had poor outcomes, with 4-year event-free survival (EFS) and overall survival (OS) of 28%, driven primarily by increased relapse risk, even among patients treated with frontline inotuzumab ozogamicin (INO) and/or blinatumomab. TP53 persistence at remission occurred in 44% of tested patients and was associated with increased ALL relapse risk. These results demonstrate that TP53 VAF is prognostic in older patients with Ph-negative B-cell ALL; high VAF may increase relapse risk but is not independently associated with survival in younger patients.

Aumolertinib plus anlotinib was effective and well-tolerated as first-line therapy in EGFR-mutant NSCLC patients with BMs. Trial Registration: ClinicalTrials.gov(identifier NCT04978753, registered July 20, 2021).

Primary and acquired MET mutations in NSCLC exhibit distinct genomic characteristics. Patients harboring concurrent EGFR mutations in NSCLC may derive less benefit from MET-TKI and ICI, whereas those harboring TP53 co-mutations tend to experience more favorable outcomes compared with TP53 wild-type NSCLC patients when treated with MET-TKI.

By mirroring theTP53diversity observed in patient tumors, this cell line panel bridges a critical gap in head and neck carcinogenesis research, enabling mechanistic dissection of GOF phenotypes and preclinical evaluation of therapies in an array of TP53mutant cell models. Its significance lies in providing a validated, annotated resource that accelerates drug discovery and clarifies the role ofTP53mutational subtypes in HNSCC development and progression, offering a framework for future translational studies in genetically complex malignancies.