Triple-Negative Breast Cancer
We have focused our attention on the drug Tamoxifen. That's a bit paradoxical, because Tamoxifen has no effect on basically breast cancers. But Tamoxifen has two activities. It's a very interesting drug. It has an activity on receptors called estrogen receptors. And the way, in which it works for the most widely treated type of breast cancer, is that it blocks the estrogen receptors.
For breast cancers that don't have estrogen receptors this is irrelevant, but even for those that do the low doses of Tamoxifen, that receptor do not actually kill the cancer cells. In order to kill them you need to get to higher levels, which work through a different mechanism.
Those higher levels have been of great interest in cancer research. There are over a dozen clinical trials on using high-dose Tamoxifen for all kinds of different cancers, although, surprisingly not for basal-like breast cancer. So, Tamoxifen has these secondary properties that looked extremely interesting to us.
Targeting Cancer Stem Cells
One of the big problems that we have in cancer research is that we know that cancers have a subset of cells, so we call cancer stem cells that are resistant to therapy. If you don't get rid of them you may get glitter for a lot of the tumor, but it just re-grows. So, you've gone to attack the cancer stem cells.
A Protein, C-Cbl, Has a Major Role in Treatment Failure
Well, it turns out that by making civil active again, we now target the cancer stem cells. So, we have a single therapy now that enables us to make the bulk tumor response of the Tamoxifen and target the cancer stem cells in that category of breast cancer that has been most difficult to treat.
How Can We Get New Treatments to the Clinic More Quickly?
In this program we always are faced with the recognition that these are urgent problems. People are dying. And the 10 year process of drug discovery has to be hastened. One of the ways, in which you hey some drug discovery, is you take all the drugs that have already been approved for other purposes. And you ask whether any of them have properties that no one has realized before.
Everyone does find these successes, because all drugs are dirty. So, all drugs have multiple properties, just like Tamoxifen has multiple properties. So, we can harness these other properties.