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Updated: Jan 22, 2026
Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
Published on: April 11, 2018
TP53 in bone and soft tissue sarcomas
Elizabeth Thoenen1, Amanda Curl2, Tomoo Iwakuma3
1Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66010, USA.
Abstract:
Genomic and functional study of existing and emerging sarcoma targets, such as fusion proteins, chromosomal aberrations, reduced tumor suppressor activity, and oncogenic drivers, is broadening our understanding of sarcomagenesis. Among these mechanisms, the tumor suppressor p53 (TP53) plays significant roles in the suppression of bone and soft tissue sarcoma progression. Although mutations in TP53 were thought to be relatively low in sarcomas, modern techniques including whole-genome sequencing have recently illuminated unappreciated alterations in TP53 in osteosarcoma. In addition, oncogenic gain-of-function activities of missense mutant p53 (mutp53) have been reported in sarcomas. Moreover, new targeting strategies for TP53 have been discovered: restoration of wild-type p53 (wtp53) activity through inhibition of TP53 negative regulators, reactivation of the wtp53 activity from mutp53, depletion of mutp53, and targeting of vulnerabilities in cells with TP53 deletions or mutations. These discoveries enable development of novel therapeutic strategies for therapy-resistant sarcomas. We have outlined nine bone and soft tissue sarcomas for which TP53 plays a crucial tumor suppressive role. These include osteosarcoma, Ewing sarcoma, chondrosarcoma, rhabdomyosarcoma (RMS), leiomyosarcoma (LMS), synovial sarcoma, liposarcoma (LPS), angiosarcoma, and undifferentiated pleomorphic sarcoma (UPS).
Insights
The tumor suppressor p53 (TP53) is crucial in preventing bone and soft tissue sarcomas. New research reveals TP53 alterations and novel therapeutic strategies for these challenging cancers.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Sarcomagenesis involves various genetic alterations, including fusion proteins and oncogenic drivers.
- The tumor suppressor p53 (TP53) is increasingly recognized for its role in suppressing bone and soft tissue sarcoma progression.
- While historically underestimated, TP53 mutations are now being uncovered in sarcomas like osteosarcoma through advanced genomic techniques.
Purpose of the Study:
- To explore the genomic and functional aspects of TP53 in nine specific bone and soft tissue sarcomas.
- To highlight the significance of TP53 alterations in sarcomagenesis and therapy resistance.
- To review emerging therapeutic strategies targeting TP53 in sarcomas.
Main Methods:
- Genomic analysis, including whole-genome sequencing, to identify TP53 alterations.
- Functional studies to understand the impact of wild-type and mutant p53.
- Review of current and novel therapeutic approaches targeting TP53.
Main Results:
- TP53 plays a critical tumor-suppressive role in osteosarcoma, Ewing sarcoma, chondrosarcoma, rhabdomyosarcoma, leiomyosarcoma, synovial sarcoma, liposarcoma, angiosarcoma, and undifferentiated pleomorphic sarcoma.
- Oncogenic gain-of-function activities of mutant p53 (mutp53) are implicated in sarcomas.
- Novel strategies targeting TP53 include restoring wild-type p53 (wtp53) activity, reactivating wtp53 from mutp53, depleting mutp53, and targeting TP53-deficient cells.
Conclusions:
- Understanding TP53 alterations is key to advancing sarcoma research.
- Emerging TP53-targeting therapies offer promise for treating therapy-resistant sarcomas.
- TP53 is a pivotal factor across a spectrum of bone and soft tissue sarcomas, presenting new therapeutic avenues.
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