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‘Gene chips’ personalize cancer treatments

It looked bad for Chuck Fleming — lung cancer had spread through his body. But his oncologist decided to try using a “gene chip” to see which out of a laundry list of chemotherapy options might work best.
/ Source: Reuters

It looked bad for Chuck Fleming — lung cancer had spread through his body. But his oncologist decided to try using a “gene chip” to see which out of a laundry list of chemotherapy options might work best.

Nine months later, Fleming is not cured, but he feels well enough to consider playing golf again and his targeted treatments — a daily pill and a twice-monthly infusion — do not make him feel weak and nauseated.

Dr. Eric Lester is convinced this personalized approach to treating cancer is the way to go in a world in which doctors now have dozens of drugs to choose from, every patient’s tumor is different, and no one has any time to waste.

Lester wants to collaborate with other oncologists to build up a database of information about the various genetic mutations seen in tumors and match them to drugs that work the best against them. Cancer experts agree gene chips are the obvious way to do this.

“It is a smarter way to treat cancer,” said Lester, of Oncology Care Associates in St. Joseph, Michigan.

Lung cancer is a serious killer — only about 15 percent of patients live for five years or more.

Most have no symptoms until the tumors have spread, making a cure nearly impossible. This is what happened with Fleming, a 63-year-old automotive consultant.

“I was consulting in Mexico and my shoulder started to hurt and I started taking ibuprofen and a couple of tequilas,” Fleming said in a telephone interview.

It took several consultations to discover he had not hurt his shoulder playing golf, but had lung cancer that had spread to his bones and his brain.

There are many options for treating lung cancer. Some are the new targeted therapies, which home in on specific genetic mutations.

They have fewer side-effects than chemotherapy. But they do not work on every tumor. Currently, doctors rely on their instincts and personal experience to choose the right ones.

Lester bought some Affymetrix gene chips — small tiles of silicon that light up to show which genes are most active in a tissue sample.

He worked with Craig Webb of the Van Andel Research Institute in Grand Rapids, Mich., who has a computer program for analyzing gene chips.

Scientists know a little about some of the genes that are over-active or under-active in cancer — genes such as EGFR, which stimulates tissue growth.

But Lester discovered why it is not so straightforward to simply read a gene chip and choose a drug. For EGFR alone, there were nine different results, five suggesting a cancer-causing mutation but four others saying little.

A drug called Avastin targets EGFR, as does a pill called Tarceva. There were some other clues that Fleming’s tumors might resist some standard chemotherapy drugs and not others.

“On that basis and recognizing that the man was faced with a very horrible disease, I chose to give him Tarceva up front,” Lester said.

But to be safe he also gave Lester a standard, but toxic, chemotherapy combination.

“There are a lot of leaps of faith involved in looking at (gene) chip data and taking that to patient care, but as a practicing clinician I can’t wait for 1,000 more experiments to be done,” Lester said.

“This man would be dead if we didn’t get lucky enough to find a chemotherapy regimen that would make him get better.”

Lester presented data on Fleming and five other patients who tried his do-it-yourself gene analysis method to a meeting of the American Association for Cancer Research in Atlanta.

The chemotherapy made Fleming’s hair fall out and he lost more than 100 pounds (50 kg) from his 300-pound frame. “It was like somebody was giving me poison. I would come home and the next day I would sit in the shower and throw up,” Fleming said.

After Fleming’s tumors shrank, Lester put him on Tarceva and Avastin alone.

“I have got a new life,” Fleming said. “I am much happier at this stage in my life than I would have been being dead from cancer.”