REVIEW article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1605080
This article is part of the Research Topicp53 in Cancer Therapy: The Impact of Mutations on the Genome GuardianView all 5 articles
Involvement of TP53 in Osteosarcoma - Challenges and Prospects
Provisionally accepted
- 1Binzhou Medical University, Binzhou, China
- 2Shandong Second Medical University, Weifang, Shandong Province, China
- 3Yantai Yuhuangding Hospital, Yantai, Shandong Province, China
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Osteosarcoma (OS), the most common primary malignant bone tumor, remains a therapeutic challenge because of its high metastatic potential, chemoresistance, and poor prognosis. Mutations in the TP53 tumor suppressor gene, including loss-of-function (LOF) and gain-of-function (GOF) mutations, play a central role in OS progression by disrupting cell cycle regulation, DNA repair, and apoptosis and promoting immune evasion and metabolic reprogramming. This review provides an in-depth analysis of p53 biology in OS, highlighting its impact on therapeutic resistance and tumor progression. We discuss advancements in radiotherapy, chemotherapy, and immunotherapy, emphasizing strategies targeting mutant TP53 and its associated pathways. Emerging approaches, including metabolic reprogramming, noncoding RNA regulation, and precision biomarkers such as miRNAs and histone modifications, offer promising tools for diagnosis, risk stratification, and treatment optimization. By linking the molecular mechanisms of p53 with novel therapeutic strategies, this review underscores opportunities for translational research aimed at improving the clinical outcomes of OS patients.
Keywords: TP53, p53, Mutation, Osteosarcoma, molecular mechanism
Received: 02 Apr 2025; Accepted: 22 Oct 2025.
Copyright: © 2025 Shen, Shu, Geng, Wang and Sui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Guang Da Wang, wgdsh123@sohu.com
Laijian Sui, herrsui@126.com
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