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TP53 in Biology and Treatment of Osteosarcoma

1
Small Animal Magnetic Resonance Imaging Laboratory, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland
2
Department of Experimental Pharmacology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland
3
Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, 02-106 Warsaw, Poland
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Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland
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Department of Soft Tissue, Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
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Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
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Laboratory of Centre for Preclinical Research, Department of Experimental and Clinical Physiology, Medical University of Warsaw, 02-097 Warsaw, Poland
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Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Valeria Visconte
Cancers 2021, 13(17), 4284; https://doi.org/10.3390/cancers13174284
Received: 10 June 2021 / Revised: 12 August 2021 / Accepted: 13 August 2021 / Published: 25 August 2021
(This article belongs to the Special Issue Targeted Treatment for Soft Tissue Sarcoma and Bone Sarcoma)
Treatment of osteosarcoma, apart from chemotherapy modifications, has not changed for approximately 30 years. Similarly, as in other tumors, mutations in the TP53 gene are often observed in osteosarcoma. In this article, we highlight the possibility of targeting p53 in the treatment of osteosarcoma. We collected data on mutations in this gene founded in patients-derived samples. We describe animals with TP53 dysfunction, which may constitute preclinical models. We put emphasis on several molecules which act on p53 protein or its activity. We also highlight gene therapy approaches. Although many of the therapies are at an early stage, they offer hope for a change in the approach to osteosarcoma treatment based on TP53 targeting in the future.
The TP53 gene is mutated in 50% of human tumors. Oncogenic functions of mutant TP53 maintain tumor cell proliferation and tumor growth also in osteosarcomas. We collected data on TP53 mutations in patients to indicate which are more common and describe their role in in vitro and animal models. We also describe animal models with TP53 dysfunction, which provide a good platform for testing the potential therapeutic approaches. Finally, we have indicated a whole range of pharmacological compounds that modulate the action of p53, stabilize its mutated versions or lead to its degradation, cause silencing or, on the contrary, induce the expression of its functional version in genetic therapy. Although many of the described therapies are at the preclinical testing stage, they offer hope for a change in the approach to osteosarcoma treatment based on TP53 targeting in the future. View Full-Text
Keywords: TP53; osteosarcoma; gene therapy; animal models; pharmacological modulation TP53; osteosarcoma; gene therapy; animal models; pharmacological modulation
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MDPI and ACS Style

Synoradzki, K.J.; Bartnik, E.; Czarnecka, A.M.; Fiedorowicz, M.; Firlej, W.; Brodziak, A.; Stasinska, A.; Rutkowski, P.; Grieb, P. TP53 in Biology and Treatment of Osteosarcoma. Cancers 2021, 13, 4284. https://doi.org/10.3390/cancers13174284

AMA Style

Synoradzki KJ, Bartnik E, Czarnecka AM, Fiedorowicz M, Firlej W, Brodziak A, Stasinska A, Rutkowski P, Grieb P. TP53 in Biology and Treatment of Osteosarcoma. Cancers. 2021; 13(17):4284. https://doi.org/10.3390/cancers13174284

Chicago/Turabian Style

Synoradzki, Kamil J., Ewa Bartnik, Anna M. Czarnecka, Michał Fiedorowicz, Wiktoria Firlej, Anna Brodziak, Agnieszka Stasinska, Piotr Rutkowski, and Paweł Grieb. 2021. "TP53 in Biology and Treatment of Osteosarcoma" Cancers 13, no. 17: 4284. https://doi.org/10.3390/cancers13174284

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