Mutant Tumor Protein p53 messenger RNA (Mutant TP53 mRNA)

Mutant Tumor Protein p53 messenger RNA (Mutant TP53 mRNA) is the transcript produced by the mutated TP53 gene, which is the most frequently altered gene in human oncology [1.3.1, 1.3.5]. While wild-type TP53 mRNA encodes a critical tumor suppressor protein that regulates DNA repair and apoptosis, the mutant mRNA variants often encode proteins that lose these protective functions and may acquire oncogenic gain-of-function (GOF) properties [1.3.1, 1.4.1]. These GOF effects contribute to increased tumor aggressiveness, chemoresistance, and poor clinical outcomes across a wide range of malignancies, including breast, lung, and hematologic cancers [1.2.1, 1.4.2, 1.4.5]. As a therapeutic target, Mutant TP53 mRNA offers a unique opportunity for precision medicine through the use of nucleic acid-based technologies [1.3.1, 1.3.3]. Strategies such as siRNA-mediated knockdown and antisense oligonucleotides (ASOs) aim to specifically degrade the oncogenic transcript or correct aberrant splicing, thereby reducing the levels of harmful mutant protein [1.2.2, 1.3.2]. Additionally, mRNA vaccines are being developed to utilize these mutant sequences as neoantigens, priming the immune system to recognize and destroy cancer cells expressing the specific p53 mutation [1.3.1, 1.3.4]. A significant challenge in targeting this molecule is the vast diversity of TP53 mutations and the critical necessity of sparing the wild-type transcript in healthy tissues to avoid systemic toxicity [1.1.2, 1.3.2].

Other names

Mutant p53 mRNATP53 mutant transcriptmtp53 mRNAMutant Tumor Protein p53 transcript

Drugs targeting mutant TP53 mRNA utilize several mechanisms, including RNA interference (RNAi) via siRNAs to silence the transcript, antisense-mediated degradation or splice correction using oligonucleotides, and the induction of immune responses through mRNA vaccines that present mutant p53 neoantigens. Additionally, certain small molecules like HDAC inhibitors can repress the transcription of the mutant gene.