TP53 in Biology and Treatment of Osteosarcoma

Cancers

Anna M. Czarnecka¹  Agnieszka Stasinska¹  Paweł Grieb¹  Piotr Rutkowski²  Wiktoria Firlej²  Ewa Bartnik³  Anna Brodziak⁴  Kamil Jozef Synoradzki⁵  Michał Fiedorowicz⁵ 

[1] Department of Experimental Pharmacology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland;Department of Soft Tissue, Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland;Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, 02-106 Warsaw, Poland;Laboratory of Centre for Preclinical Research, Department of Experimental and Clinical Physiology, Medical University of Warsaw, 02-097 Warsaw, Poland;Small Animal Magnetic Resonance Imaging Laboratory, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland;

关键词: TP53;    osteosarcoma;    gene therapy;    animal models;    pharmacological modulation;   

DOI  :  10.3390/cancers13174284

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown