According to researchers at the US National Cancer Institute, adding a second medication to tamoxifen, a breast cancer medicine used effectively for over twenty years, helps it preserve its full strength.
Ultimately, tamoxifen can lose its usefulness. But the new molecule, known as disulfide benzamide or DIBA, could offer a way to overcome that acquired resistance and bring back effectiveness of tamoxifen.
DIBA "is not a new molecule," said William Farrar, head of the Cancer Stem Cell Section of the US National Cancer Institute’s Centre for Cancer Research at Frederick, Md., and the lead author of the research. "It’s been around a while."
Compound slowed growth of tumor
Farrar’s team gave DIBA to mice engineered in order to develop tamoxifen-resistant tumors and then to human breast cancer cells in the laboratory. Tumor growth decelerated in both cases.
The results of this research are published in the December issue of Cancer Cell.
Tamoxifen is the norm of care for women who suffer from the condition known as "oestrogen-receptor positive breast cancer." When oestrogen binds to the oestrogen receptor, a cascade of events promoting rapid cell division takes place. If that cell appears to be a breast cancer cell, the series of events can cause tumor growth.
Tamoxifen works by blocking the effects of oestrogen on breast tissue. It is customarily used in the cases of advanced breast cancer or as supplementary therapy after primary treatment for early-stage breast cancer.
In Farrar’s research, when DIBA was added to the mix, tamoxifen with no trouble inhibited the growth of breast cancer cells.
Helps switch off receptors
DIBA "switches off everything, all the molecular machinery of oestrogen receptors, which leads to death of breast cancer cell," Farrar explained. What’s more, in the human breast cancer cell lines, "we got a ninety per cent decline in tumors," he added. In the mice research, DIBA decreased tumor volume almost fifty per cent.
Farrar said that DIBA is what is called a "lead" compound, which means it only opens the door to suitable medication. DIBA itself "is perhaps not suitable for humans, due to solubility problems." Farrar and his colleagues will try to develop or discover another compound more appropriate for human use, fashioning it after the properties of DIBA.
As the study progresses from the laboratory to human clinical trials, "our objective is to develop a molecule that can be administered orally," Farrar stated.
Beset with resistance problems
V. Craig Jordan, vice president and scientific director of the medical science division of the Fox Chase Cancer Centre in Philadelphia, views the new study as hopeful. Jordan, who is known as the "father of tamoxifen," remarks that tamoxifen is life-saving but also beset with resistance problems.
For instance, Jordan said, "if a hundred of women had advanced breast cancer, twenty per cent would have oestrogen-receptor negative [cancer], and tamoxifen would not be suggested. Eighty per cent would be oestrogen-receptor or ER positive, and forty per cent would experience an initial response from tamoxifen while forty per cent would not. Of the forty women [who got a response], finally all would get acquired resistance. It would take two to five years for that to happen."
Jordan claims that the NCI team "have created a possibility to move from the laboratory to the clinic." Finally, he explained, a DIBA-like compound might enhance responses in those who acquired tamoxifen resistance and probably in those who originally did not respond to tamoxifen at all.
Nevertheless, the current study, concentrated only on acquired resistance, not initial or intrinsic resistance, he said.
Jordan also said that next, the compound or a similar compound needs to be tested in humans.
