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Investigators: M. T. Schreeder, R. A. Figlin, J. J. Stephenson, L. Campos, S. P. Chawla, D. R. Spigel, A. Spira
Abstract 14565: Phase 1 report from a multicenter trial of perifosine (PERI) + sunitinib (SUT) in patients with advanced cancers including renal cell carcinoma.
Investigators: P. Allerton, B. Ebrahimi, M. T. Schreeder, P. Kaiser, S. P. Chawla
Abstract 16083: Preclinical rationale for combination targeted therapy in advanced clear cell renal cell carcinoma (RCC): Abrogation of rapamycin-mediated induction of AKT phosphorylation by perifosine.
Investigators: W. S. Holland, P. C. Mack, D. R. Gandara, P. N. Lara
KRX-0401 (Perifosine) Mechanism of Action and Profile
KRX-0401 (Perifosine) is a novel, potentially first-in-class, oral
anti-cancer agent that modulates Akt and a number of other key signal
transduction pathways, including the JNK and MAPK pathways, all of which
are pathways associated with programmed cell death, cell growth, cell
differentiation and cell survival. The effects of perifosine on Akt are of
particular interest because of the importance of this pathway in the
development of most cancers, the evidence that it is often activated in
tumors that are resistant to other forms of anticancer therapy, and the
difficulty encountered thus far in the discovery of drugs that will inhibit
this pathway without causing excessive toxicity. High levels of activated
Akt (pAkt) are seen frequently in many types of cancer and have been
correlated with poor prognosis in patients with soft-tissue sarcoma,
gastric, hepatocellular, endometrial, prostate, renal cell, head and neck
cancers and hematological malignancies, as well as glioblastoma. The
majority of tumors expressing high levels of pAkt were high-grade, advanced
stage or had other features associated with poor prognosis. High pAkt is
often seen in tumors that are
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