Cell Cycle 2008-12-15

You never know: Cdk inhibitors as anti-cancer drugs.

Tim Hunt

文献索引：Cell Cycle 7(24) , 3789-90, (2008)

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摘要

Ever since it emerged that cyclin-dependent protein kinases catalyzed cell cycle transitions and with cancer seen as "a disease of the cell cycle," people have pursued the aim of testing kinase inhibitors as anti-cancer drugs. Quite early on, Laurent Meijer and his colleagues discovered roscovitine as a potent inhibitor of Cdk1 and the compound went into clinical trials (as CYC202 or Seliciclib) whose outcomes are awaited. It was never clear to me that cancer was really a disease of the cell cycle (strictly speaking--considering that cancer cells have no trouble dividing), or how inhibiting cell cycle progression could reveal a window of therapeutic advantage between normal and neoplastic cells. Everyone knows what happens if you permanently block cell division in humans: they die. Yet, at the same time as harboring doubts about the rationale for using anti-Cdk drugs for cancer therapy, I would also be the first to admit that our understanding of cell cycle control is so far from complete, that, given the relative ease of developing specific protein kinase inhibitors, it is not a bad idea to try and see if they have selective effects on tumors. You never know.