OSTEOSARCOMA OF THE SPINE — MODERN CLASSIFICATION, THE ROLE OF THE mTOR SIGNALING PATHWAY, PROSPECTS FOR THERAPY (LITERATURE REVIEW)
Abstract
Despite their rare occurrence, spinal tumors pose a serious problem for public health due to the difficulty of their diagnosis and treatment. Neoplasms of the spine are divided into primary and secondary tumors (metastases) by origin. Osteosarcoma is of great interest among primary tumors. Osteosarcoma is a malignant osteogenic tumor consisting of neoplastic cells that produce osteoid. Osteosarcoma of the spine develops quite rarely, however, it is characterized by a high degree of malignancy, local aggressiveness, a tendency to metastasis, as well as a long asymptomatic course. The prognosis for osteosarcoma of the spine remains extremely unfavorable. All this indicates the need to develop new methods and treatment regimens for osteosarcoma. One of the promising areas is the development of drugs that affect the intracellular signaling pathway mTOR. mTOR is a serine/threonine protein kinase that forms a catalytic subunit of two different protein complexes: mTORC1 and mTORC2. It has been established that this signaling pathway regulates the processes of vital activity of the cell and the entire organism at the deepest level. Its hyperactivation plays an important role in carcinogenesis, including in the pathogenesis of osteosarcoma. In this regard, it was proposed to use drugs that affect the mTOR signaling pathway for its therapy. Such drugs include: rapamycin, everolimus, temsirolimus, catalytic inhibitors of mTOR (MLN0128 and PP242), micro-RNA (miR-223 and miR-101), oleanolic acid, spautin-1, metformin and so on. It is proposed to combine these drugs with classical chemotherapy to achieve better results in the treatment of osteosarcoma. At the moment, it is necessary to select rational combinations and dosages of drugs.
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