It was an ordinary surgery to remove a tumor — until doctors turned off the lights and the patient’s chest started to glow. A spot over his heart shined purplish pink. Another shimmered in a lung. They were hidden cancers revealed by fluorescent dye, an advance that could soon transform how hundreds of thousands of operations are done each year.
Surgery has long been the best way to cure cancer. If the disease recurs, it is usually because stray tumor cells were left behind or others lurked undetected, but there is no good way for surgeons to tell what is cancer and what is not. They look and feel for defects, but good and bad tissue often seem the same.
Now, dyes are being tested to make cancer cells light up so that doctors can cut them out and give patients a better shot at survival.
Illustration: Mountain People
With dyes, “it’s almost like we have bionic vision,” said Sunil Singhal, a doctor at the University of Pennsylvania. “We can be sure that we’re not taking too much or too little.”
The dyes are experimental, but advancing quickly. Two are in late-stage studies aimed at winning US Food and Drug Administration approval.
Johnson & Johnson just invested US$40 million into one and US federal grants support some of the work.
“We think that this is so important. Patients’ lives will be improved by this,” said Paula Jacobs, an imaging expert at the US National Cancer Institute.
In about five years, “there will be a palette of these,” she said.
Singhal was inspired a decade ago, while pondering a student who died when her lung cancer recurred soon after he thought that he had removed it all. He was lying next to his baby, gazing up at fluorescent decals.
“I looked up and saw all these stars on the ceiling and I thought, how cool if we could make cells light up” so people would not die from unseen tumors, he said.
A dye called Indocyanine green had long been used for various medical purposes. Singhal found that when big doses were given by intravenous therapy a day before surgery, it collected in cancer cells and glowed when exposed to near infrared light. He dubbed it TumorGlow and has been testing it for lung, brain and other tumor types.
He used it on Ryan Ciccozzi, a 45-year-old highway worker and father of four from Deptford, New Jersey, and found hidden cancer near Ciccozzi’s heart and in a lung.
“The tumor was kind of growing into everything in there,” Ciccozzi said. “Without the dye, I don’t think that they would have seen anything” besides the baseball-sized mass visible on CT scans.
Singhal is also testing a dye for On Target Laboratories, based in a Purdue research park in Indiana, that binds to a protein more common in cancer cells. A late-stage study is underway for ovarian cancer and a mid-stage one for lung cancer.
In one study, the dye highlighted 56 of 59 lung cancers seen on scans before surgery, plus nine more that were not visible ahead of time.
Each year, about 80,000 patients in the US have surgery for suspicious lung spots.
If a dye could show that the cancer was confined to a small node, the surgeons could remove a wedge instead of a whole lobe and preserve more breathing capacity, On Target chief executive officer Marty Low said.
No price has been set, but dyes are cheap to make and the cost should fit within rates that hospitals negotiate with insurers for these operations, he said.
Dyes might hold the most promise for breast cancer, said Len Lichtenfeld, a doctor with the American Cancer Society.
Up to one-third of women who have a lump removed need a second operation because margins were not clear — an edge of the removed tissue later was found to harbor cancer.
“If we could drop that down into the single digits, the impact would be huge,” said Kelly Londy, who heads Lumicell, a suburban Boston company testing a dye paired with a device to scan the lump cavity for stray cancer cells.
A device called MarginProbe is sold now, but it uses different technology to examine the surface of tissue that has been taken out, so it cannot pinpoint in the breast where residual disease lurks, said Barbara Smith, a breast surgeon at Massachusetts General Hospital.
She leads a late-stage study of Lumicell’s system in 400 breast cancer patients. In an earlier study of 60 women, it revealed all of the cancers, verified by tissue tests later.
However, it also gave false alarms in more than one-quarter of the cases — “there were some areas where normal tissue lit up a little bit,” Smith said. “Still, you would rather take a little extra tissue with the first surgery rather than missing something and have to go back.”
Blaze Bioscience is testing Tumor Paint, patented by company cofounder Jim Olson of the Fred Hutchinson Cancer Research Center and Seattle Children’s Hospital. It is a combo product — a molecule that binds to cancer and a dye to make it glow.
“You can see it down to a few dozen cells or a few hundred cells,” Olson said. “I’ve seen neurosurgeons come out of the operating room with a big smile on their face because they can see the cancer very clearly.”
Early-stage studies have been done for skin, brain and breast cancers in adults, and brain tumors in children.
Avelas Biosciences of San Diego has a similar approach: A dye attached to a molecule to carry it into tumor cells. The company is finishing early studies in breast cancer and plans more for colon, head and neck, ovarian and other types.
Cancer drugs have had a lot of attention, while ways to improve surgery have had far less, company president Carmine Stengone said.
“This was just an overlooked area, despite the high medical need,” Stengone said.
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