@article {ST{\"U}HMER453, author = {THORSTEN ST{\"U}HMER and KAMOL ISKANDAROV and ZHENHAI GAO and THOMAS BUMM and EVELYN GRELLA and MICHAEL R. JENSEN and HERMANN EINSELE and MANIK CHATTERJEE and RALF C. BARGOU}, title = {Preclinical Activity of the Novel Orally Bioavailable HSP90 Inhibitor NVP-HSP990 against Multiple Myeloma Cells}, volume = {32}, number = {2}, pages = {453--462}, year = {2012}, publisher = {International Institute of Anticancer Research}, abstract = {Background: HSP90 inhibitors effectively reduce expression and activity levels of oncogenic survival proteins. However, their clinical anti-multiple myeloma (MM) activity has been found to be rather weak, spurring the exploration of combination therapies and development of compounds with improved physicochemical properties. Materials and Methods: Preclinical effects of the novel orally bioavailable HSP90 inhibitor NVP-HSP990 on the viability, apoptosis and client protein levels of MM cells (established cell lines and clinical specimens) were tested alone and in combination with other drugs. Results: NVP-HSP990 exerted profound activity against MM cells, with a molecular mode of action conforming well with its role as HSP90 inhibitor. Enhanced activity was most obvious in combination with melphalan. Combination with a phosphatidylinositol-3-kinase (PI3-kinase)/mammalian target of rapamycin (mTOR) inhibitor, rendered the HSP90 blockade-mediated stress response ineffective and considerably increased the anti-MM toxicity. Conclusion: Given the current interest in both HSP90 and PI3-kinase/mTOR as potential clinical targets, these observations could broaden the therapeutic utility of either class of inhibitor in MM.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/32/2/453}, eprint = {https://ar.iiarjournals.org/content/32/2/453.full.pdf}, journal = {Anticancer Research} }