Tumor cell biologists have identified a new way of overcoming breast cancer cells that are resistant to current drugs. The researchers presented their findings at the 33rd annual San Antonio Breast Cancer Symposium in December 2010.

Shiuan Chen, right, and Cynthie Wong may have found a way to overcome a certain form of drug resistance in breast cancer cells. (Photo by Darrin S. Joy)

Shiuan Chen, Ph.D., director of the Division of Tumor Cell Biology, and Cynthie Wong, student in the Irell & Manella Graduate School of Biological Sciences, found a strategy for killing breast cancer cells that are resistant to drugs called aromatase inhibitors.

Aromatase inhibitors block the enzyme aromatase, which the body uses to make the hormone estrogen.

Most breast cancers require estrogen to grow, and these cancer cells often generate large amounts of aromatase, so they can produce endless supplies of estrogen for themselves. But using aromatase inhibitors to choke off this supply of estrogen starves the breast cancer cells.

“Inhibiting aromatase is an important tactic for treating estrogen-dependent breast cancers,” said Chen. Currently, three aromatase-inhibiting drugs are approved by the U.S. Food and Drug Administration.

Unfortunately, he noted, many breast cancers become resistant to aromatase inhibitors over time, enabling cancer to return and spread. Some other breast cancers arise with drug resistance already built in.

Searching for strategies to regain the upper hand on these resistant cancers, Chen and Wong turned to the lab to focus on 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 cells need to thrive,” Wong said. “Blocking HSP90 would prevent proper folding of those other proteins and weaken the cancer cells.”

To find if they were on the right track, they grew aromatase inhibitor-resistant breast cancer cells in the laboratory, and then added an experimental drug that inhibits HSP90. They found the drug prevented the cells from growing.

They also exposed the cells to an aromatase inhibitor and the HSP90 inhibitor together, and the results were encouraging: The combined anticancer effect was greater than expected from adding the cancer-fighting power of each alone.

“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 continue to explore HSP90 inhibition in hopes of moving the therapy to clinical trials.