Rola i potencjał terapeutyczny sfingolipidowego szlaku sygnalizacyjnego w nowotworach hematologicznych

Abstract

One of the key obstacles in the progress of cancer treatment is the lack of balance between the uncontrolled proliferation and cell apoptosis. It is now known that sphingolipids are essential molecules regulating the processes of growth, differentiation and death of living cells. Depending on their chemical nature, sphingolipids may have a stimulatory (S1P, sphingosine-1-phosphate) or inhibitory (ceramide) effect on cellular proliferation. A number of different studies have shown that the generation of ceramide in response to cytotoxic therapy is an important element leading to cell death. Cancer cells use different methods limiting the production of ceramides that leads to their removal. The effect of oncogenic S1P results from its stimulating effect on DNA synthesis and chemotactic mobility of the vascular endothelial cells and angiogenesis. The use of monoclonal anti-S1P antibodies is potentially a valuable therapeutic option for inhibiting angiogenesis determining the growth of tumors. It was additionally demonstrated that S1P beyond the direct and indirect by stimulating the release of vascular endothelial growth factor and basic fibroblast growth factor angiogenic action has an effect on tumor growth and its metastatic potential. Among the sphingolipids, ceramide was identified first as inducing differentiation and the death of human HL-60 promyelocytic leukemia cells. Progress in understanding the role of sphingolipids was regarded until recently as the only structural component of cell membranes allowing the use in the treatment of complex properties of this group of signaling molecules. Thus, it has become important to clarify the role of sphingolipids in the regulation of the balance between proliferation signals/ /survival rate and death of cells in order to develop new therapies for neoplastic diseases of myeloid and lymphoid origin.