Pharmacologist Donald McDonnell, from Duke University Medical Center, Durham, N.C., says one of the newly designed compounds is ready for human trials, which are slated to start next year in advanced cancer. It if works, the new compound will provide long-term protection from cancer, he says. He predicts that these compounds will eventually replace tamoxifen, which loses its cancer fighting powers in about two to five years. In a recent issue of the journal Science, the researchers, from Duke University Medical Center, Durham, N.C., trace the resistance problem to a molecule on breast cancer cells known as the estrogen receptor. This molecule brings the cancer-boosting hormone into the cell.
Tamoxifen blocks the estrogen receptor, thus starving the tumor.
But, says McDonnell, protection from tamoxifen is short-lived because the estrogen receptor changes shape after a few years of exposure to the drug. He says breast cancer cells learn to see tamoxifen as an estrogen. The once life-saving drug, McDonnell says, starts feeding the tumor. The estrogen receptor creates this resistance by forming pockets on the cell surface that change the way tamoxifen affects the tissues. It changes from a tumor killer to a kind of a cancer promoter.