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Cracking Cancer’s Secret Code: Oncologist Searches for Breast Cancer’s Achilles’ Heel

Over the last decade, oncologist Jennifer Pietenpol has been trying to decode and kill a difficult-to-treat type of breast cancer. Known as triple-negative breast cancer, this form of the disease can be highly aggressive and resistant to chemotherapy.

The cancer, which accounts for 10 to 20 percent of all breast cancers in the United States, is also a deadly genetic riddle that doctors find easiest to describe in terms of what it is not. “Between 75 to 85 percent of breast cancers express one of three clear targets for therapy,” says Pietenpol, who runs the Vanderbilt-Ingram Cancer Center in Nashville, Tenn. “But with triple-negative cancer, there is nothing to attack and patients go into a standard of care that involves combinations of chemotherapy that have been determined by experiment. We felt that in this era of precision medicine, we should get a better handle on the treatment.”

Pietenpol and her team have collected and analyzed more than 600 cases of triple-negative breast cancer so far, and their results have defined six biological subtypes of the disease. This breakthrough could help scientists apply existing drugs and procedures to attack the cancer, develop new ones, and map out treatment.

Last year, GE’s Healthymagination Challenge, an open innovation quest that seeks to find and fund the best new ideas in breast cancer detection and treatment, gave Pietenpol’s team $100,000 to finance more science. “We are beginning to get that molecular information from an individual patient’s tumor,” she says. “This is helping us guide therapy and align it with patients. Every bit of additional funding helps to accelerate this further.”

Doctors divide breast cancer into four groups, based on what is driving tumor growth. The vast majority of breast cancers use the estrogen receptor, the progesterone receptor or the HER2 pathway for growth. “When we see this, we can apply existing therapy, like Tamoxifen,” Pietenpol says.

Her research group and other teams are now looking for similar tools and targets to destroy the fourth type of breast cancer, triple-negative cancer. “Our task is to understand how these tumor cells grow, find their Achilles’ heel, and how we can hit it,” she says.

Pietenpol starts by looking at the different pathways the tumor cells appear to use to signal growth, pairs that information with genetic data about how the cells mutate and then tests the hypotheses in her lab. “In cancer, we want to move to predictive oncology where we can use molecular information to better guide treatment,” she says.

Pietenpol’s team has already pinned six unique targets to triple-negative cancer’s back. One of them, an androgen receptor, could expose as many as 10 percent of triple-negative cancer cases to attack. But additional targets will likely be smaller. “As we go more into precision medicine, the fraction of people with any given molecular subtype will get smaller and smaller,” she says. “This is where we are going, using much more precision therapy where no two tumors are going to be alike.”

Pietenpol’s team has started designing clinical trials for each of the six subtypes. She says that “androgen-receptor antagonists” used for treating prostate cancer could be effective against the androgen receptor subset her team discovered. “We are continuing to accelerate this, but we have a lot of work to do,” she says. “We’ve just begun to uncover these lower hanging fruits.”

Triple-negative breast cancer has been defined by what it is not, but Dr. Jennifer Pietenpol and her team has identified six different subtypes of the disease.

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