TP53 wild-type

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.

Total cell-bound activity, rather than added activity, better predicted radiotoxicity in both TP53-wild-type and TP53-null cell lines, indicating that its therapeutic effect is primarily governed by PSMA-mediated uptake rather than p53 status. These results support the therapeutic potential of [212Pb]Pb-AB001 across cells with varying TP53 status and suggest that combining [212Pb]Pb-AB001 with DNA repair or checkpoint inhibitors may enhance treatment efficacy.

Therefore, studying other HSP40/JDPs that are involved in the advancement of cancer and the activities of p53 (both mutant and wild type), together with their related processes, would enhance our understanding of how cancer progresses, we might potentially speed up the development of innovative treatments for cancer. It is expected that pharmacological molecules and their analogues that specifically target p53 aggregation might be utilised with other anticancer drugs to address the issue of p53 aggregation.

Among increasingly personalised strategies, particular promise is shown by HER2-targeted therapies for HER2-positive malignancies (e.g. trastuzumab deruxtecan). Additionally, targeting TP53 wild-type tumours with selinexor, as well as addressing AKT and DNA repair pathways in both uterine carcinomas and sarcomas (i.e. AKT inhibitor and poly(ADP-ribose) polymerase inhibitor combinations), represents key advancements. Furthermore, anti-angiogenic and immune checkpoint inhibitor combinations hold significant promise for future therapeutic strategies.

Collectively, our findings delineate a multifaceted mechanism whereby olivomycin A coordinates EMT suppression, apoptotic induction, and mitochondrial clearance. Thus, olivomycin A has potential as a therapeutic candidate that can target both survival and metastatic pathways in heterogeneous genetic backgrounds.

P1, N=266, Completed, Boehringer Ingelheim | Active, not recruiting --> Completed

The system demonstrated potential as a safe and effective therapeutic agent in an orthotopic xenograft hepatocellular carcinoma (HCC) model where it inhibited the degradation of the p53 protein. In conclusion, the study introduced an innovative systemic peptide delivery system in which peptides delivered by scAAVs effectively block tumorigenic intracellular PPIs, providing a promising strategy for cancer therapy.

Forty (60.6%) of the 66 patients experienced progression of disease and subsequently received second-line therapy. Only 61% of patients with metastatic EGFR -mut NSCLC received second-line therapy after osimertinib at our institution, confirming that the second-line therapy rates in the control arm of FLAURA2 are similar to practice patterns at our US academic medical center.

These data were supported by a significant reduction in proliferation and a decrease in Ki-67 expression. Our 3D models closely resemble retinoblastoma tumor tissue and can serve as a platform to assess innovative drugs or implement the promising results on the use of MDM2 inhibitors for retinoblastoma treatment.