Tumor protein p53 pathway component messenger RNAs (p53 pathway mRNAs)

The p53 pathway is a critical cellular defense mechanism that maintains genomic integrity by regulating cell cycle progression, DNA repair, and programmed cell death (MDPI, 2025). In a vast majority of human cancers, this pathway is inactivated either through direct mutations in the TP53 gene or through the overexpression of its negative regulators, such as MDM2 and MDM4 (Science Translational Medicine, 2019). Targeting the messenger RNAs (mRNAs) of these pathway components has emerged as a promising therapeutic strategy to reactivate tumor suppression. This approach encompasses two primary modalities: the delivery of synthetic, wild-type TP53 mRNA to restore functional p53 protein in p53-null or p53-mutant tumors, and the use of RNA interference (siRNA) or antisense oligonucleotides (ASOs) to knockdown the mRNAs of p53 inhibitors like MDM2 (Nature Communications, 2022; AACR, 2025). Unlike traditional gene therapy, mRNA-based interventions do not require nuclear entry or genomic integration, reducing the risk of insertional mutagenesis while providing a transient and dose-controllable therapeutic effect (NIH, 2025). Clinical and preclinical candidates, such as mRNA-2525 and various MDM2-targeting siRNAs, are currently being evaluated for their ability to sensitize tumors to chemotherapy and immunotherapy (AACR, 2024).

Other names

TP53 pathway mRNAsp53-related messenger RNAsMDM2/MDM4 mRNAsp53 signaling network mRNAs

Restoration of tumor suppressor protein function via synthetic mRNA translation or silencing of oncogenic regulators via RNA interference (siRNA) or antisense oligonucleotides (ASOs).