Novel Approaches for Detecting TP53 Mutations and Targeted Therapeutic Strategies: Emerging Insights Into Cytoplasmic p53 Aggregates in Ovarian Cancer
ABSTRACT
Background
Ovarian cancers have been the most lethal gynecologic malignancies worldwide, with survival outcomes remaining poor despite therapeutic advances. Since TP53 is the most frequently mutated gene in ovarian cancers, it highlights the central role of p53 dysfunction in promoting tumor initiation, genomic instability, and progression. Beyond classical loss of transcriptional activity, mutant p53 may exert dominant‐negative effects on residual wild‐type protein and acquire oncogenic gain‐of‐function properties that promote invasion, metastasis, and resistance to chemotherapy. Nevertheless, despite extensive efforts, effective therapeutic agents targeting TP53 ‐mutant tumors remain elusive, representing a major unmet medical need.
Methods
The published articles were reviewed.
Results
To detect the TP53 mutations, driven by recent technological innovations, circulating tumor DNA has emerged as a powerful and minimally invasive biomarker that enables the detection of gene mutations and the real‐time monitoring of tumor evolution, minimal residual disease, and therapeutic resistance. Bridging diagnostics and therapy, recent discoveries highlight that cytoplasmic p53 aggregates as a clinically adverse phenotype in high‐grade serous ovarian cancers, elucidating mechanisms of aggregate formation and propagation. By restoring p53 conformation and transcriptional activity through distinct molecular mechanisms, pharmacologic reactivation of mutant p53 holds promise as a novel therapeutic strategy.
Conclusion
These advances indicate that TP53 disruption, once deemed untargetable, may become a new cornerstone of precision oncology in ovarian cancer.