TP53 wild-type

These findings establish a mechanistic link between hormonal signaling, p53 allelic status, and m6A-dependent post-transcriptional regulation. Although further in vivo validation is required, disruption of the ALKBH5-REG1A axis may contribute to heterogeneous endometrial responses to tamoxifen, thereby providing a conceptual framework for biomarker-oriented investigation.

P1/2, N=78, Not yet recruiting, University College Dublin

We conducted a single-center retrospective study of 69 patients treated with Tisagenlecleucel, to evaluate the prognostic impact of TP53 alterations (TP53Alt), including mutations and/or deletions...These findings identify TP53 alterations as a strong adverse prognostic factor in patients with r/r B-ALL treated with CAR-T therapy. Screening for TP53Alt may guide risk-adapted strategies, including early consolidation with hematopoietic stem cell transplantation or alternative therapies.

The PARP inhibitor talazoparib (TAL) combined with the alkylating agent temozolomide (TMZ) produces synergistic cytotoxicity selectively in mtp53, but not wild-type p53 (wtp53), breast cancer cells and organoids. These findings reveal a previously unrecognized mechanism by which the mutant p53-PARP axis enables replication stress tolerance and drives cancer metastasis. We show mutation of p53 in TNBC provides an additional biomarker-guided framework to improve PARPi therapeutic outcomes.

Silencing p53 also failed to affect simvastatin-induced cell cycle arrest or impact the sensitivity of MB cells treated with simvastatin in combination with hypoxia, X-ray or azacitidine, an epigenetic therapy with DNA methyltransferase inhibition. Collectively, our findings indicate that MVP function is independent of p53 in MB.

Mapping of the impact of chemoradiation on cellular interactions in cervical cancer reveals how treatment reshapes the tumor microenvironment and highlights targets for developing future immunotherapeutic approaches. See related commentary by Klopp, p. 1540.

TP53 mutations appear to be an independent prognostic marker for prolonged progression-free survival in patients with metastatic colorectal cancer. Although the difference in overall survival was not statistically significant, these findings warrant further validation in prospective studies to confirm the prognostic utility of TP53 in therapeutic stratification.

The spirooxindoles 6b, 6k, and 6n attained the most pronounced activity in the MULTI-ARRAY MDM2-p53 complex assay with IC50 values of 1.26, 1.30, and 1.25 µM, respectively, in comparison with nutlin-3 (IC50 = 2.03 µM)...Molecular docking and molecular dynamics simulations justified the observed efficacy. Collectively, this study showcased a new class of potent p53-MDM2/MDMX dual inhibitors possessing a spirooxindole scaffold which can be subjected to future development.

After carboplatin and paclitaxel treatment, a combination chemotherapy used in human LUSC, we detected increased neutrophils in circulation, spleen and tumors, and increased Bcl-xL in neutrophils and TANs. Bcl-xL blockade decreased the pool of Bcl-xL-high TANs and synergized with chemotherapy. Altogether, our results suggest distinct outcomes for targeting TANs in different tumor types and reinforce the concept of repurposing BH3 mimetics against cancer.

Residual function did not affect prognosis in patients with single-hit mTP53 (median OS: 24.9 months vs. 16.1 months; P = 0.985), and prognosis did not differ between patients with GOF mTP53 and those with non-GOF mTP53 (median OS: 9.5 months vs. 9.8 months; P = 0.913). Quantitative abnormalities in the TP53 gene affected prognosis, suggesting that qualitative abnormalities did not.

Patients with TP53 mutations had poor outcomes, with OS of 9.1 months in monoallelic (HR for death 0.88 with SCT, p = 0.69) and 6.8 months in biallelic (HR for death 0.76 with SCT, p = 0.14). SCT can lead to excellent long-term survival in TP53-wild type HR MDS.

She completed six cycles of adjuvant chemotherapy (paclitaxel + carboplatin, TC regimen). No recurrence was observed during follow-up. This case underscores the importance of considering PPC in the differential diagnosis of pelvic masses in young females, even when the ovaries appear normal.