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Review

Molecular Biology of Osteosarcoma

1
Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland
2
Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Institute—Oncology Centre, 02-781 Warsaw, Poland
3
Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
4
Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, 02-106 Warsaw, Poland
5
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland
6
Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 02-097 Warsaw, Poland
7
Small Animal Magnetic Resonance Imaging Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland
8
Interinstitute Laboratory of New Diagnostic Applications of MRI, Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, 02-109 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Contributed equally.
Cancers 2020, 12(8), 2130; https://doi.org/10.3390/cancers12082130
Received: 30 June 2020 / Revised: 29 July 2020 / Accepted: 30 July 2020 / Published: 31 July 2020
(This article belongs to the Special Issue Bone and Soft Tissue Tumors)
Osteosarcoma (OS) is the most frequent primary bone cancer in children and adolescents and the third most frequent in adults. Many inherited germline mutations are responsible for syndromes that predispose to osteosarcomas including Li Fraumeni syndrome, retinoblastoma syndrome, Werner syndrome, Bloom syndrome or Diamond–Blackfan anemia. TP53 is the most frequently altered gene in osteosarcoma. Among other genes mutated in more than 10% of OS cases, c-Myc plays a role in OS development and promotes cell invasion by activating MEK–ERK pathways. Several genomic studies showed frequent alterations in the RB gene in pediatric OS patients. Osteosarcoma driver mutations have been reported in NOTCH1, FOS, NF2, WIF1, BRCA2, APC, PTCH1 and PRKAR1A genes. Some miRNAs such as miR-21, -34a, -143, -148a, -195a, -199a-3p and -382 regulate the pathogenic activity of MAPK and PI3K/Akt-signaling pathways in osteosarcoma. CD133+ osteosarcoma cells have been shown to exhibit stem-like gene expression and can be tumor-initiating cells and play a role in metastasis and development of drug resistance. Although currently osteosarcoma treatment is based on adriamycin chemoregimens and surgery, there are several potential targeted therapies in development. First of all, activity and safety of cabozantinib in osteosarcoma were studied, as well as sorafenib and pazopanib. Finally, novel bifunctional molecules, of potential imaging and osteosarcoma targeting applications may be used in the future. View Full-Text
Keywords: osteosarcoma; molecular mechanisms; targeted therapy; theranostics; tumor initiating cells; molecular imaging osteosarcoma; molecular mechanisms; targeted therapy; theranostics; tumor initiating cells; molecular imaging
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MDPI and ACS Style

Czarnecka, A.M.; Synoradzki, K.; Firlej, W.; Bartnik, E.; Sobczuk, P.; Fiedorowicz, M.; Grieb, P.; Rutkowski, P. Molecular Biology of Osteosarcoma. Cancers 2020, 12, 2130. https://doi.org/10.3390/cancers12082130

AMA Style

Czarnecka AM, Synoradzki K, Firlej W, Bartnik E, Sobczuk P, Fiedorowicz M, Grieb P, Rutkowski P. Molecular Biology of Osteosarcoma. Cancers. 2020; 12(8):2130. https://doi.org/10.3390/cancers12082130

Chicago/Turabian Style

Czarnecka, Anna M., Kamil Synoradzki, Wiktoria Firlej, Ewa Bartnik, Pawel Sobczuk, Michal Fiedorowicz, Pawel Grieb, and Piotr Rutkowski. 2020. "Molecular Biology of Osteosarcoma" Cancers 12, no. 8: 2130. https://doi.org/10.3390/cancers12082130

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