TUMOR RECURRENCE AND TAMOXIFEN RESISTANCE: WHAT MAKES A CELL RESISTANT TO TAMOXIFEN?

Many cellular changes have been associated with the development of tamoxifen resistance, but we still do not fully understand the basis of this clinical problem. After prolonged tamoxifen exposure a selection process may favor cells that have no estrogen receptors 01 cells that produce abnormal or aberrant receptors that fail to recognize tamoxifen. Because tamoxifen is known to have estrogenic effects, scientific studies have shown that estrogenic metabolites of tamoxifen may contribute to the development of cellular resistance to tamoxifen. As in other types of drug resistance, there may be some form of cellular pump that removes tamoxifen from the cell.Other research has focused on the involvement of proteins known as growth factors. Because tamoxifen is understood to increase the release from certain cells of the growth-inhibitory factor known as TGF-b, tamoxifen resistance may also occur when these cells can no longer produce the TGF-b required to continue restraining growth of the breast cancer cells.Much of this new information is speculative, yet it does suggest that several different mechanisms may contribute to the development of tamoxifen resistance. All require further investigation.*43\320\2*