Failed Drugs Expose Preclinical Blunders

Once a promising cancer treatment, the failure of PARP inhibitors in the clinic may be due to flawed preclinical studies.

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WIKIMEDIA COMMONS, TOM VARCO

In January 2011, a phase III clinical trial for a highly touted new cancer therapy called iniparib, which inhibits a class of DNA-repair proteins called poly(ADP-ribose) polymerases, or PARPs, failed to prolong survival in metastatic breast cancer patients. Then in December, another leading PARP inhibitor, olaparib, performed poorly in a phase II clinical trial against ovarian cancer. Prior to large clinical trials, both drugs had shown promising, though unpublished, preclinical results, and were considered the “next big thing” in cancer therapy. But after the two failures, “clinicians were saying they didn't want to open any more clinical trials of PARP inhibitors,” Scott Kaufmann, a researcher at the Mayo Clinic in Rochester, Minnesota, told Nature.

So Kaufmann’s lab took a closer took at iniparib. Their results, ...

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