Tests for Tumor DNA in Blood May Yield New Ways to Hit Cancer

2/26/14Follow @tanseyverse

What do blood cancers, HIV infection, and cardiovascular disease have in common?

Drug developers made rapid progress in those three disease categories once they had blood tests that could monitor changes in individual patients as they responded to medications, says Helmy Eltoukhy, CEO of Redwood City, CA-based diagnostics startup Guardant Health.

But that progress hasn’t been matched for solid tumors such as lung cancer and breast cancer, where blood tests are limited, Eltoukhy says. Doctors may keep relying on an initial biopsy to identify the genetic mutations driving the uncontrolled growth of cells. But new mutations continue to arise in the fast-growing cancer cell population, and the therapy that worked at first often fails in time.

Further biopsies could guide the next series of treatment choices, but biopsy surgery is expensive, and often too risky in already sick patients. That can leave prescribing doctors flying blind.

“You can’t fight an enemy you can’t see,” Eltoukhy says. (Eltoukhy is pictured below between Guardant co-founder AmirAli Talasaz at right and Guardant chief financial officer Michael Wiley.)

Guardant Health Executive Team

Guardant Health Executive Team

Guardant emerged from stealth mode recently to unveil its solution to the problem: a blood test that analyzes the genetic traits of tumor cell DNA that circulates in the bloodstream. The aim is to improve treatment by predicting which therapies may work.

The company is focusing on breast, lung, colorectal, skin and prostate tumors—a roster of top cancer diagnoses. Very specific blood tests already exist for known genetic “hot spots” in particular cancers, but Guardant’s broader test is an attempt to capture mutations that might come as a surprise.

The company’s “pan-cancer” blood test, Guardant360, was designed to detect mutations in 54 genes that are already the targets of either approved drugs or those in late-stage testing. The purpose is to produce tests results that are “actionable”—where the discovery of a specific mutation would suggest that a certain therapy may be effective or ineffective.

The dozens of genes tested include EGFR, the target of the antibody drugs cetuximab (Erbitux) from Imclone and Amgen’s panitumumab (Vectibix), used to treat colorectal cancer; and HER2, the target of the Genentech/Roche antibody drugs trastuzumab (Herceptin) and pertuzumab (Perjeta), used to treat breast cancer.

Guardant has already been working with top cancer centers—it won’t disclose all the names yet—and the test has been used to sequence samples from hundreds of patients, Eltoukhy says. He describes one patient who illustrates the outcome Guardant is aiming for. A 62-year-old metastatic melanoma patient who hadn’t benefitted from three previous therapies was tested and found to have a mutation that’s already targeted by another drug. After eight weeks on the new treatment, the patient’s tumors had shrunk by 90 percent, Eltoukhy says.

“Those kinds of things can happen when we have real-time information,” Eltoukhy says. “That’s not going to be the case with every patient.”

The Guardant360 test will be tweaked over time, he says. For example, the panel of genes tested can be expanded as new cancer drugs are approved to attack new targets.

“The weapons you have to attack the disease become that much richer,” he says.

Guardant’s technology is a challenge to a group of other companies that have also been vying to create a broader cancer blood test—a so-called “liquid biopsy” that would eliminate the need for repeated biopsy surgeries. Rather than testing for free tumor DNA in the blood, these competitors have created various mechanisms to isolate the rare, intact tumor cells circulating in the bloodstream, so their genes can be analyzed. It’s been a challenging technical task for the companies, which include Epic Sciences of San Diego, CA; Houston,TX-based ApoCell; and Johnson & Johnson unit Janssen Diagnostics of Raritan, NJ, which markets the CellSearch system.

There may only be a single tumor cell amid hundreds of millions of normal blood cells, according to Menlo Park, CA-based SRI International, which recently announced the commercial availability of its own FASTcell testing service to detect and analyze circulating tumor cells from blood samples.

Eltoukhy wonders whether the few intact tumor cells captured are representative of the total population of cancerous cells in the patient. Rather than isolating whole cells, Guardant instead tests the blood for fragments of tumor DNA released from cancer cells that have died and broken apart. “There’s so much more material in the cell-free domain,” he says.

While whole circulating tumor cells are rare, tumor DNA in the blood is also scarce—about one part of tumor DNA for every 199 parts of DNA from non-cancer cells. Guardant’s test relies on … Next Page »

Bernadette Tansey is a freelance journalist based in Berkeley, CA. Follow @tanseyverse

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