University of Rochester boffins discover possible new key to breast cancer treatment in later stages.

Certain types of cancers seem to show resistance to treatments that in earlier stages are very effective. An example of this is the breast cancer fighting drug known as Tamoxifan. In early stages, it is a standard drug to prescribe because of its effectiveness. But in later stages, it appears to have no effect whatsoever.

University of Rochester researchers believe they have isolated the difference between the two stages that causes this stymie. They have isolated a specific protein. that seems to make the difference. And with it, they may have discovered a way to extend the treatment of breast and other forms of cancer well beyond the early stages:

Led by doctoral student Hsing-Yu Chen and Mark Noble, Ph.D., professor of Biomedical Genetics at URMC, the team studied the molecular mechanism that allows basal-like breast cancer cells to escape the secondary effects of tamoxifen, and discovered that two proteins are critical in this escape. One protein, called c-Cbl, controls the levels of multiple receptors that are critical for cancer cell function. A second protein, Cdc42, can inhibit c-Cbl and is responsible for the tumor’s underlying resistance.

The team also discovered that targeting Cdc42 – and thus inhibiting the inhibitor – with an experimental drug compound known as ML141 restored c-Cbl’s normal function. Through additional work in animal models and in human cell cultures, the team demonstrated that when ML141 is paired with tamoxifen, it enhances the ability of tamoxifen to induce cancer cell death and suppress the growth of new cancer cells. Neither drug alone had the same effect on basal-like breast cells.

So in the future, a one / two punch of Tamoxifan and ML141 may be the program of choice when dealing with this difficult cancer.