Some, but not all, breast cancer cells have specific receptors that bind estrogen molecules circulating in the bloodstream. When estrogen binds to the estrogen receptor, it triggers a series of events that promote cell division. If the cell is a breast cancer cell, this interaction leads to tumor growth. In women with estrogen receptor-positive cancers, cancer cell growth is strongly influenced by estrogen.
Tamoxifen works by binding to estrogen receptors in place of estrogen and blocking the signals that lead to cell division. Initially, tumor growth slows or stops altogether. With continued tamoxifen treatment, however, the estrogen receptor and the estrogen-dependent signaling pathways in the cell can become altered, rendering tamoxifen ineffective as an inhibitor. In some cases, tamoxifen begins to act like estrogen and can stimulate tumor growth.
DIBA and related compounds are being studied because of their ability to disrupt cellular activity at the genetic level. These so-called electrophilic compounds were first investigated for possible use against AIDS because they can block the human immunodeficiency virus (HIV) from replicating. The HIV studies are ongoing.
"This basic study generated exciting results in our mouse model and suggests a promising approach that might be tried in human patients," said Farrar. His laboratory is now exploring ways to produce DIBA in a form that is water soluble so it could be administered as a pill, the same as tamoxifen. If successful, this could set the stage for preclinical studies.
Collaborators on the research include Georgetown University, Washington, D.C., Baylor College of Medicine and The Methodist Hospital, Houston, Texas, and the National Institute of Allergy and Infectious Diseases, Bethesda, Md.
