Tanespimycin as Antitumor Therapy

Background:The 90 kDa heat shock protein (HSP90), which facilitates proper folding and stability of numerous signaling molecules involved in growth control, cell survival, and development, has been implicated in malignant processes. Like its parent compound geldanamycin, tanespimycin binds to HSP90 and causes antineoplastic effects in vitro and in vivo.Materials and Methods:All relevant published papers identified through searches of PubMed and abstracts from major recent hematology and oncology meetings were reviewed as of October 2009.Results:Different formulations and schedules of tanespimycin monotherapy and combination therapy have been tested in several phase I studies in patients with solid tumors or multiple myeloma (MM). No responses have been reported in studies of tanespimycin monotherapy in patients with metastatic melanoma. Tanespimycin given in combination with trastuzumab in patients with metastatic breast cancer induced a partial response in 24% of patients. Single-agent tanespimycin showed activity in MM and in combination with bortezomib, 27% of patients achieved minor response or better (48% bortezomib-naive patients, 22% bortezomib-pretreated patients, 13% bortezomib-refractory patients).Conclusion:Tanespimycin represents a promising new agent for the treatment of relapsed/refractory MM. Results of ongoing and future trials will determine the role of tanespimycin both in MM and other malignancies, including breast cancer.