Breast cancer researchers are nothing if not persistent. Despite the disease’s ability to find new ways of surviving, these scientists maintain an unwavering commitment to regaining the upper hand.
 Shiuan Chen, right, and Cynthie Wong may have found a new way to knock down some therapy-resistant breast cancers. (Photo by Darrin S. Joy) |
Take the case of aromatase, for instance. Aromatase is an enzyme that helps make the hormone estrogen, which most breast cancers love. In fact, they need it to grow and thrive. So these breast cancers produce a lot of aromatase and make their own endless supply of estrogen.
But scientists caught on to this trick and targeted aromatase with new drugs, aiming to choke off this supply of estrogen and starve breast cancer cells. The tactic has been fairly successful. Currently, three aromatase-inhibiting drugs are approved by the U.S. Food and Drug Administration.
But the drugs haven’t been perfect. Many breast cancers become resistant to aromatase inhibitors over time, which enables the cancer to return and spread. And some other breast cancers arise with drug resistance already built in.
So researchers found a new angle that might fight these resistant cancers.
Shiuan Chen, Ph.D., director of City of Hope’s Division of Tumor Cell Biology, and Cynthie Wong, a student in the Irell & Manella Graduate School of Biological Sciences at City of Hope, turned their sights to a possible new drug target called heat shock protein 90, or HSP90.
A so-called “chaperone” protein, HSP90 helps other proteins fold themselves into the correct three-dimensional shape they need to function.
HSP90 interacts with quite a few proteins that breast cancer cells need to thrive, according to Wong. “Blocking HSP90 would prevent proper folding of those other proteins and weaken the cancer cells.”
To find if they were on the right track, the scientists went to the lab and grew breast cancer cells that they knew could resist aromatase inhibitors. Then, they added an experimental drug that inhibits HSP90. It seemed to work. The drug prevented the cells from growing.
Next, they tried exposing those resistant cells to an aromatase inhibitor and the HSP90 inhibitor together. The results were encouraging: The drugs appeared to work together synergistically. That is, the combined anticancer effect was actually greater than expected from simply adding together each drug’s cancer-fighting power.
“Our study demonstrates that HSP90 inhibitors can be used in conjunction with aromatase-inhibitor therapy, which could both extend the treatment period for these patients before the cells develop resistance as well as potentially treating drug-resistant tumors,” Chen said.
The researchers are continuing their efforts to block HSP90 in hopes of moving the therapy to clinical trials.
