Herceptin pioneer’s life science innovation: Cancer pathways should be treatment focus

by Kim Lamb Gregory

From:: MedCity News

Breast cancer research pioneer Dr. Dennis Slamon says the way doctors view and treat cancer needs a theoretical shift, and he is about to roll out research that will light the way toward this new framework.

“This is the paradigm shift we are going to be rolling out over the next two to five years,” said Slamon, who is chief of the division of hematology oncology and holds several other titles at the David Geffen School of Medicine at UCLA.

Salmon is the researcher who developed the chemotherapy drug trastuzumab, or Herceptin, which has made a big difference in survival outcomes for women with a specific type of breast cancer.

The research is embargoed so Slamon could not be specific, but said he plans to roll out new data at the 2013 San Antonio Breast Cancer Symposium in December that will show ways to get better survival outcomes for women with a HER2/neu positive breast cancer.

HER2/neu is short for a protein called human epidermal growth factor receptor 2, which promotes the growth of cancer cells.

Before Slamon developed Herceptin and it was approved for use in 1998, the prognosis for women with HER2/neu breast cancer was poor, with only 26 percent free from recurrence or death in two to five years. Recent data now shows five year survival at 84 percent.

“We think we can do even better,” Slamon said. “We have new data we will present in a month that has taken it from 84 percent to 92 percent.”

Salmon and a panel of five doctors and a therapist who deal with cancer appeared before standing-room-only crowd Thursday night at the Lundring Events Center on the California Lutheran University campus.

One in five to one in six women will develop breast cancer, he said, adding that one in two men and one in three women will develop some sort of cancer in their lifetime.

Cancer is not a single disease, Slamon said, and even cancer in the same organ — such as breast cancer — is not the same disease from person to person.

“Previously, we treated breast cancer with a one-size-fits-all approach based on where the cancer occurred,” Slamon told the audience.

Each woman’s breast cancer is different, Slamon told the audience, and he believes doctors would have even more success diagnosing and treating cancer based on what type of pathways it uses to spread, rather than based on which organs are affected.

What is true for breast cancer could also be true for other cancers like lung, ovarian, prostate and colon cancer.

To put a complicated process as simply as he could, Slamon explained cancer as what happens when a cell makes a mistake when it is replicating genes. The cell becomes “broken,” he said, if a gene is copied incorrectly.

“It must copy that gene with complete fidelity. Mistakes can’t get made. And if mistakes are made … in these critical genes that regulate all this growth, you can be off to the races with the process we know as cancer,” Slamon said.

The HER2/neu protein is dangerous because it attaches itself to the outside of a cell and can transfer broken signals — molecule to molecule — to the nucleus of a cell, not unlike a TV antenna on top of a roof used to transfer signals down through cables into the TV.

“Trastuzumab, or Herceptin is like a blanket thrown over the antenna,” Slamon said.

“What we’ve done traditionally — and it has been effective for many, many patients — is throw in nonspecific bombs in hopes to kill more of these rapidly proliferating cells than normal cells that are also proliferating,” Slamon said, referring to most standard chemotherapy treatment, which can result in unpleasant side effects.

Slamon believes there is promise in treating other cancers much the way he has attacked HER2/neu positive breast cancer — with specific, targeted chemotherapy.

Research has advanced to the point where doctors may be able to get enough information from each different type of tumor — no matter which organ develops the tumor — so doctors can figure out what is broken on a genetic level, then concoct and deliver a specific, targeted cocktail of drugs to shut down the signal pathway and receptors the cancer is using to divide and spread.

Salmon said there may be not one cure, but many cures for cancer based on what it broken. The possibility, he said, is there.

Panelist Dr. Paul Miller — a radiation oncologist with North Oaks Radiation Oncology Medical Center in Thousand Oaks — said Slamon’s work with the HER2/neu gene is what launched the movement toward targeted therapy.

“Hopefully, Dr. Slamon will get his Nobel Prize,” Miller said. “He’s long overdue.”