In a recent issue, Mesri et al. reported that the apoptosis inhibiting protein survivin can be inhibited in a wide variety of tumor cells using a dominant negative form of the protein. Survivin is expressed normally in early development and is found in tumors of many sorts, but few healthy adult cell types express it. Especially in larger and more advanced tumors, cancer cells can become dependent on survivin for their continued proliferation, apparently because this protein abolishes a normal cell-cycle checkpoint and prevents them from being driven toward apoptosis. Zaffaroni et al. now show that hammerhead ribozymes directed at the survivin mRNA have a similar, potentially beneficial effect. Such ribozymes can synergize with a more traditional chemotherapeutic, cisplatin, to kill human melanoma cells in culture. This finding is particularly interesting in light of a recent report in the Journal of the National Cancer Institute (Kanwar, J.R., et al. 2001. 93:1541?1552.), showing that inhibition of survivin using antisense or dominant negative transgenes helps eliminate established lymphomas and prevent the emergence of new tumors in a mouse model. Ribozymes to survivin might therefore be used in a similar manner, probably in conjunction with chemotherapeutic or immunotherapeutic agents, to control human tumors in a clinical setting.

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Contact: John Ashkenas
scied@the-jci.org
416-946-7593
Journal of Clinical Investigation
16-Jan-2002

Page: 1
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