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News Note: Perifosine Effective in Treatment of Neuroblastoma Tumors in Mice

Posted May 12 2010 9:00pm
News Note: Perifosine Effective in Treatment of Neuroblastoma Tumors in Mice

Perifosine, an oral anticancer agent and potent inhibitor of a protein known as AKT, may be effective in the treatment of neuroblastoma, one of the most common and deadly forms of childhood cancer. NCI researchers found that perifosine dramatically inhibited neuroblastoma growth, and in one case caused tumor regression in mice implanted with human neuroblastoma tumor cells. This work builds on a series of studies started almost a decade ago in which NCI investigators mapped the AKT signaling pathways that mediate neuroblastoma resistance to chemotherapy, survival under stress conditions, invasive capability, and stimulation of new blood vessel formation that is required for tumor growth. It is also known that AKT levels are higher in the tumors of neuroblastoma patients who have the worst prognosis for survival.

Another important finding of this study relates to the recent identification of mutations in the receptor protein ALK. There are targeted agents for ALK that are in clinical trials. While these targeted agents have been quite effective in pre-clinical studies, some mutations are not responsive to inhibitors and some tumors may develop resistance over time. In this study, scientists found that the growth of neuroblastoma tumors containing ALK mutations, or over-expression of ALK, is inhibited by perifosine. In some tumor cells AKT is a target of ALK. Researchers are beginning to appreciate that signaling systems within cells are interconnected and AKT may be a critical connection in sensing signals from multiple pathways. Thus inhibition of AKT may block multiple growth stimulating signaling pathways in tumor cells. The study was published online, May 12, 2010, in the Journal of the National Cancer Institute, and is available at http://jnci.oxfordjournals.org/cgi/content/abstract/djq125 .

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