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• W1488755767 abstract "Malignant melanoma, once disseminated, is a malignant neoplasm extremely resistant to conventional anticancer treatment, such as chemo or radiation therapies. Therefore, new therapeutic strategies are under investigation as, for instance, immunotherapy, gene therapy or so called targeted therapy. Proteasome appears as one of these new possible targets. The ubiquitin proteasome pathway is a complex multicatalytic system specialized in the degradation of proteins of intracellular origin, unlike lysosomes that are specialized in the degradation of proteins of extracellular origin. Many of the proteins degraded by the proteasome are molecules involved in cell proliferation and apoptosis, such as cyclins and cyclin dependent kinases, the proapoptotic protein p53 or the nuclear transcription factor NFkappaB. It has been demonstrated that inhibition of proteasome induces cell death, more strongly in neoplastic cells than in normal cells, and, even more, that proteasome inhibition sensitizes neoplastic cells to other proapoptotic stimulus such as chemo o radiation therapy, probably by the NFkappaB pathway. Therefore, the proteasome could be a good target for cells so resistant to apoptosis as melanoma cells are. We and others have demonstrated that melanoma cells are sensitive in vitro to Bortezomib and other proteasome inhibitors, that are able to decrease melanoma cell viability, to induce a reduction in cell proliferation rate and a cell cycle arrest and to trigger apoptotic cell death through both caspase dependent and independent pathways. Bortezomib is a commercially available proteasome inhibitor, mainly used for the treatment of multiple myeloma and other malignant hematological disorders. Although the only published phase II clinical trial using single agent Bortezomib in patients with advanced melanoma yielded disappointing results, the potential use of proteasome inhibitors for the treatment of metastatic melanoma patients is still under assessment. Based on the knowledge of the physiological role of the proteasome system and on preclinical studies, employment of proteasome inhibitors in combined therapies seems the best way to afford the use of these compounds for advanced melanoma treatment." @default.
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• W1488755767 date "2011-06-30" @default.
• W1488755767 modified "2023-10-18" @default.
• W1488755767 title "Targeting the Proteasome in Melanoma" @default.
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• W1488755767 doi "https://doi.org/10.5772/19099" @default.
• W1488755767 hasPublicationYear "2011" @default.
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