M ouse xenograft models of cancer, understandably, have a terrible reputation. Although researchers and companies routinely use these human tumors in mice for preclinical drug testing, individual models poorly predict how drugs will act in the clinic. Retrospective re views published by the National Cancer Institute in 2001 and the National Cancer Institute of Canada in 2003 came to the same conclusion: Drugs that work against cancer in xenograft mice rarely work in people with the same tumor, with the exception of lung and possibly ovarian cancer.“There’s this mantra:‘Xenografts don’t predict for human effects,’” said Peter Houghton, Ph. D., a cancer researcher at the St. Jude Children’s Research Hospital in Memphis, Tenn.

But not all xenograft models poorly predict drug effects. In direct transfer, or “explant,” xenografts, recently dubbed “tumorgrafts,” tumors taken from patients are chopped into fragments slightly smaller than a pencil eraser and implanted directly into immunodeficient, or “nude,” mice.(Standard xenografts use permanent cell lines, not primary tumors, as the source of tumor material.) In several retrospective studies, drug effects in such mice closely mirror human effects when differences in drug activity between species are taken into account.“They work extremely well, as long as you factor in the drug systemic exposure,” Houghton said.