Communicating science: Sharon Cantor discusses drug resistance in breast, ovarian cancer

Sharon Cantor, PhD, professor of molecular, cell & cancer biology, studies inherited breast and ovarian cancer. Her research examines the gap in understanding how chemotherapy works.

Dr. Cantor said when patients learn they have cancer, they hope to hear their doctor say that there is a drug that will kill only the tumor. In precision medicine, the doctor understands specific genetic information about the patient’s cancer and can select drugs that target it.

“People are really excited about precision medicine especially when it comes to treating hereditary breast and ovarian cancers,” Cantor said.

These cancers are thought to be vulnerable to drugs that cut the tumor DNA in half like a chainsaw.

“Despite all this drug tumor knowledge, people are suffering,” Cantor said. “Sometimes chemotherapy does not work, or the therapy ultimately fails, and the patients die. Something in our knowledge for cancer and the drugs we’re using to treat cancer must be wrong.”

Cantor compared the study of cancer drug resistance to astronomer Galileo Galilei. When he discovered that planets don’t revolve around the earth but rather the sun, he faced lots of pushback. Her “Galileo moment” was finding out her data ultimately didn’t support the model that chemotherapy works by breaking the DNA in half.

The old model looked clear cut: cancer cells killed by chemo showed defects in fixing broken DNA and cancer cells surviving showed the ability to fix broken DNA. But this correlation appeared to fall short when the Cantor lab studied a large set of cancer cells. Moreover, Cantor and her colleagues looked at the tumor DNA bombarded with toxic chemotherapy and found little evidence that the DNA was actually cut in half. Instead, they saw the tumor DNA riddled with holes.

“Rather than a chainsaw, the chemo was acting more like a woodpecker, and the woodpecker holes accumulated through chemotherapy treatment,” Cantor said. “The cancer cell next became very sick and like a dead tree, fell over and broke apart.”

Later, it appeared the old chainsaw model was based on dying or already dead cancer cells, so the fragile DNA with the holes were key in chemotherapy killing the tumor. When cancers learn how to defend against chemotherapy and became chemo-resistant, Cantor found that they eventually filled the holes, and their DNA became solid again.

“This understanding will allow us to make drugs that maximize DNA holes and combine them with drugs that prevent tumors from making their DNA solid again and chemo-resistant,” Cantor said. “Together, these will ensure chemotherapy targets vulnerable tumors and fully succeeds in killing the tumor. It’s another chapter in the book of cancer genetics where a long-held belief is overturned.”