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Release Date: September 17, 2007
Termination Date: September 17, 2008
Several new therapeutic agents that target the PI3K/AKT pathway in tumor cells are becoming available. These agents include inhibitors of the downstream cytoplasmic protein kinase, mTOR. Oncologists and oncology nurses who have an interest in new biologics need to understand the regulation of this pathway, how dysregulation contributes to carcinogenesis, and why inhibitors of mTOR may have efficacy in certain malignancies.
Inhibitors of mTOR have been most thoroughly evaluated in metastatic renal cell carcinoma (RCC), a tumor highly resistant to traditional chemotherapeutic agents. In RCC, the VHL tumor suppressor gene pathway is inactivated, which results in increased vascularization. This sensitizes these tumors to the antiangiogenic effects of mTOR inhibition. Emerging clinical research suggests that mTOR inhibitors may also have efficacy in other solid tumors, including some in which the PTEN tumor suppressor gene is inactivated, and in hematologic malignancies. Oncologists and oncology nurses need to be informed of the clinical end points and adverse events associated with using mTOR inhibitors to treat these tumor types. Only from understanding both the molecular and the clinical data will oncologists and oncology nurses be able to assess the value of using mTOR inhibitors in optimizing patient management and meeting current standards of care.
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Robert J. Motzer, MD, is Professor of Medicine at Weill Medical College of Cornell University in New York City. Additionally, Dr Motzer is Attending Physician in the Division of Solid Tumor Oncology at Memorial Hospital for Cancer and Allied Diseases and Member of the Memorial Sloan-Kettering Cancer Center, both in New York City.
Dr Motzer received his medical degree from the University of Michigan Medical School, Ann Arbor, and completed a residency in internal medicine at Cornell University Medical College, Affiliated Hospitals of North Shore University Hospital, Manhasset, New York, and Memorial Sloan-Kettering Cancer Center. He completed fellowships in medical oncology/hematology and research at Memorial Sloan-Kettering Cancer Center and in medicine at Cornell University Medical Center.
A genitourinary medical oncologist, Dr Motzer focuses on testicular and kidney cancers. He is the leading researcher for a multisite clinical trial of high-dose chemotherapy for patients with germ-cell tumors and a poor prognosis. Dr Motzer also conducts trials of paclitaxel in patients with relapsing or nonresponsive testicular cancer and of new immunotherapy and chemotherapy drugs for treatment of kidney cancer.
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