The evolving role of TP53 mutation in hepatocellular carcinoma (HCC)
- 1Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, 430060 China
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancer types globally, which is characteristically aggressive, with a poor prognosis and a high mortality rate. The pathways leading to the development and progression of this fatal disease have been studied at the macro and micromolecular levels, where the interplay of multiple factors has been observed in multistep processes. Invariably, all factors at some point trigger mutations in specific genes that contribute to the development and progression of hepatic tumors. Decades of research have demonstrated that, among all genetic variations, mutation in the TP53 gene is the most frequent phenomenon, attracting global interest in cancer research. Driven by certain external and internal factors, the mutation transforms TP53 into an active oncogene with both gain-of-function (GOF) and loss-of-function (LOF) properties, collectively exerting a robust carcinogenic effect. The key mechanisms involved in this process include the P53-MDM2 negative feedback loop, the CDK4/cyclin D1-PIN1-FBW7a-c-Myc axis, profound immune modulation, and the development of cancer stemness, collectively shaping tumor behavior. Given that patients with p53 mutations often present with advanced-stage, it is crucial to adopt mutation-centric subgroup stratification to achieve prognostic precision and therapeutic success. However, emerging techniques are facing significant challenges due to the diverse heterogeneity and immune modulation caused by the mutation, making it difficult to design an effective management scheme. In recent years, several strategies have shown promising results in preclinical and early clinical settings, and combining them with established frontline therapies or incorporating them into preventive measures may open new possibilities. Existing studies largely highlight the mutation from molecular and clinicopathological perspectives, rather than undertaking an inclusive examination and meaningful translation for prospective clinical advancement. This review attempts to fully capture the unfolding role of p53 mutations, primarily based on the literature from the last 10 years, and provides a comprehensive perspective on both mechanistic insights and translational aspects.
Related
- Open, laparoscopic, and robotic liver resection for hepatocellular carcinoma: evolving roles, comparative outcomes, and future perspectives
- Tumour Mutation Burden Does Not Predict Immune Cell Frequency or Risk of Recurrence After Surgery in Hepatocellular Carcinoma.
- Impact of different TP53 mutation subtypes on response and outcome in advanced lung adenocarcinoma receiving first-line immunotherapy or chemo-immunotherapy
- Context‐Dependent TP53 Mutation Gain‐of‐Function Is Correlated With Its Contribution to Genomic Instability
- Combined Point Mutation in a Single Allele of the TP53 Gene Potentiates the Oncogenic and Transcriptional Properties of TP53 in Lung Cancer.
BibTeX
@article{rahman2026evolving,
title = {{The evolving role of TP53 mutation in hepatocellular carcinoma (HCC)}},
author = {Md Rafee Ur Rahman and Xin Chen and Ananya Podder and Ximing Xu},
journal = {Cancer Cell International},
year = {2026},
month = jul,
doi = {10.1186/s12935-026-04408-x},
url = {https://doi.org/10.1186/s12935-026-04408-x},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - The evolving role of TP53 mutation in hepatocellular carcinoma (HCC)
AU - Md Rafee Ur Rahman
AU - Xin Chen
AU - Ananya Podder
AU - Ximing Xu
PY - 2026
DA - 2026/07/31
JO - Cancer Cell International
DO - 10.1186/s12935-026-04408-x
UR - https://doi.org/10.1186/s12935-026-04408-x
AB - Hepatocellular carcinoma (HCC) is one of the most common cancer types globally, which is characteristically aggressive, with a poor prognosis and a high mortality rate. The pathways leading to the development and progression of this fatal disease have been studied at the macro and micromolecular levels, where the interplay of multiple factors has been observed in multistep processes. Invariably, all factors at some point trigger mutations in specific genes that contribute to the development and progression of hepatic tumors. Decades of research have demonstrated that, among all genetic variations, mutation in the TP53 gene is the most frequent phenomenon, attracting global interest in cancer research. Driven by certain external and internal factors, the mutation transforms TP53 into an active oncogene with both gain-of-function (GOF) and loss-of-function (LOF) properties, collectively exerting a robust carcinogenic effect. The key mechanisms involved in this process include the P53-MDM2 negative feedback loop, the CDK4/cyclin D1-PIN1-FBW7a-c-Myc axis, profound immune modulation, and the development of cancer stemness, collectively shaping tumor behavior. Given that patients with p53 mutations often present with advanced-stage, it is crucial to adopt mutation-centric subgroup stratification to achieve prognostic precision and therapeutic success. However, emerging techniques are facing significant challenges due to the diverse heterogeneity and immune modulation caused by the mutation, making it difficult to design an effective management scheme. In recent years, several strategies have shown promising results in preclinical and early clinical settings, and combining them with established frontline therapies or incorporating them into preventive measures may open new possibilities. Existing studies largely highlight the mutation from molecular and clinicopathological perspectives, rather than undertaking an inclusive examination and meaningful translation for prospective clinical advancement. This review attempts to fully capture the unfolding role of p53 mutations, primarily based on the literature from the last 10 years, and provides a comprehensive perspective on both mechanistic insights and translational aspects.
SN - 1475-2867
ER -