TP53 (Tumor protein P53)

Based on preclinical studies showing synergism with simultaneous inhibition of the estrogen receptor (ER), CDK4/6 and PI3K pathways and based on window of opportunity studies showing that metformin suppresses PI3K/mTOR signaling in endometrial cancer (EC), we conduct a non-randomized phase 2 study of letrozole/abemaciclib/metformin in ER positive endometrioid EC (NCT03675893). There are no objective responses among TP53 mutated ECs and among NSMP (no specific molecular profile) tumors with RB1 or CCNE1 alterations; CTNNB1 mutations correlate with clinical benefit. Pharmacokinetic analyses demonstrate that administration of letrozole and abemaciclib with metformin result in a more than 3-fold increase in metformin exposure.

This study demonstrates the feasibility of localized tumor-normal sequencing in Nigerian BC patients, revealing actionable variants with clinical relevance. These findings highlight the need to integrate genomic profiling into routine cancer care and establish molecular tumor boards to advance precision oncology in Nigeria.

The core action targets of curcumin are MMP9, TP53, MYC and TNF, among others, and its key signaling pathways are PI3K/AKT, tumor and other signals, and so on, so that multi-component, multi-targets, and multi-pathways exert its therapeutic effects on OSF. By elucidating the multi-target mechanism of action of curcumin, our study offers a new theoretical basis for the clinical therapy strategy of OSF.

In summary, the dacarbazine-2-AEH2P combination exhibits synergistic pharmacodynamic activity that enhances cytotoxicity through coordinated modulation of proliferative and apoptotic pathways. These findings highlight its potential as a promising strategy to improve chemotherapeutic efficacy and overcome resistance in melanoma treatment.

P2, N=160, Active, not recruiting, French Innovative Leukemia Organisation | Recruiting --> Active, not recruiting | Trial primary completion date: Jan 2026 --> Aug 2025

These findings provide critical insights into early tumorigenesis, highlighting the potential of precursor cells as biomarkers for early detection and therapeutic targets of esophageal squamous cell cancer. By elucidating the cellular dynamics underlying esophageal preneoplasia, this research lays the foundation for strategies to prevent malignant progression, offering broader implications for improving cancer diagnostics and treatment approaches.

This novel combination of ATR inhibitor berzosertib with irinotecan did not lead to objective responses in patients with TP53-mutated, advanced gastroesophageal adenocarcinoma. The combination regimen was well tolerated without unexpected adverse events. This trial was registered with ClinicalTrials.gov (NCT03641313).

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.

It may be prudent to maintain increased vigilance for persistent vulvar lesions, particularly in HPV-negative and histologically ambiguous settings. Comprehensive assessment (including immunohistochemistry) may facilitate earlier detection and more accurate diagnosis, thereby potentially improving treatment outcomes.

Consistently, expression of IL-15 resulted in blockade of tumor progression in the TKP CCA model. These findings highlight the importance of oncogenic Kras in CCA tumor maintenance and underscore KRAS inhibition as a potential therapeutic approach for CCA.

PINK1 acts as a tumor suppressor in colorectal cancer by inhibiting proliferation and migration, promoting apoptosis, and remodeling the epigenetic landscape through altering histone modifications and enhancing chromatin accessibility.

P1/2, N=32, Active, not recruiting, Bambino Gesù Hospital and Research Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2025 --> Mar 2027