Cellular tumor antigen p53 (mutant) (mutp53)

Mutant TP53 refers to the altered forms of the cellular tumor antigen p53, a critical transcription factor often called the guardian of the genome (UniProt P04637). In its wild-type state, p53 regulates the cell cycle, DNA repair, and apoptosis to prevent tumor development (PubMed: 29451101). However, mutations in the TP53 gene—found in over 50% of human cancers—not only result in the loss of these tumor-suppressive functions but often confer gain-of-function (GOF) properties that actively promote tumor progression, metastasis, and drug resistance (Nature Reviews Cancer, 2019). Therapeutic strategies targeting mutant p53 focus on restoring its original tumor-suppressive conformation or selectively eliminating the mutant protein (Cancer Discovery, 2021). Given its prevalence across diverse malignancies, mutant p53 is a high-priority target for precision oncology, with several small-molecule reactivators like Eprenetapopt and Rezatapopt currently in clinical trials (ClinicalTrials.gov).

Other names

Mutant p53Tumor protein p53 (mutant)TP53 mutantp53 mutant

Therapeutic approaches include the use of small molecules to restore the wild-type conformation and transcriptional activity of the mutant protein, promoting the degradation of the mutant protein through the ubiquitin-proteasome system, or inhibiting its oncogenic gain-of-function interactions with other transcription factors (PubMed: 32814821).