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Czarnecka, Anna M; Synoradzki, Kamil; Firlej, Wiktoria; Bartnik, Ewa; Sobczuk, Pawel; Fiedorowicz, Michal; Grieb, Pawel; Rutkowski, Piotr
Cancers, 07/2020, Volume: 12, Issue: 8Journal Article
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. 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 gene in pediatric OS patients. Osteosarcoma driver mutations have been reported in , , , , , , and 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.
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