October’s Breast Cancer Awareness Month activities remind us of the progress science has made in the fight against the disease. Regular mammograms and better diagnostics find cancers earlier. Combined with better therapies, these advances mean more women are surviving.
But breast cancer is wily and still finds ways of resisting and bypassing treatment. Fortunately, researchers at City of Hope and their scientific partners aren’t backing down in their fight against the disease.
|Susan Kane and colleagues study mechanisms of drug resistance. (Photo by Markie Ramirez)|
Take the case of the anticancer drug Herceptin.
Herceptin works by targeting a protein called Her2. Some breast cancer cells overproduce Her2, which sets off a chain of events that keeps the tumor cells growing and thriving. Herceptin interferes with Her2, bringing cancer growth to a standstill.
About a fourth of patients with breast cancer have high levels of Her2, making Herceptin a strong treatment option for them. Herceptin can be effective in up to 70 percent of those patients, depending on the exact stage of the cancer and the other drugs physicians combine with it.
Sadly, most of the cancers become resistant to Herceptin within a year, and they start growing again. Scientists believe these resistant breast cancer cells find another way to trigger the chain of events required for continued growth: a sort of back door to survival when the front door — Her2 — is closed.
Enter researchers in City of Hope’s Division of Tumor Cell Biology.
Professor Susan E. Kane, Ph.D., and her team found that one possible key to breast cancer’s backdoor survival lies in a pair of related proteins, DARPP-32 and t-DARPP.
First, the researchers found that Herceptin-resistant breast cancer cells have higher levels of t-DARPP than cells that respond to Herceptin. The protein might somehow help the cells survive, they thought.
The scientists took cells that normally respond to Herceptin and artificially increased the amount of t-DARPP in those cells. They exposed the cells to Herceptin and found the cells kept growing — just like cells naturally resistant to Herceptin.
Researchers think that t-DARPP might give cells a way to bypass Her2 and find a different road to growth.
The good news is that the team may have found a way to block the escape route. When they increased the amount of t-DARPP’s chemical cousin, DARPP-32, the cells became sensitive to Herceptin again.
“DARPP-32 definitely counteracts t-DARPP’s effect,” said Kane, “and this also gives us a clue about the alternative path that those two proteins interact with in affecting response to Herceptin.”
Although she cautioned that more work is needed to fully understand the biochemical processes involved, Kane noted that the finding could point the way toward new drug targets that may overcome Herceptin resistance.