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Microchip device monitors lung cancer cells 7-3-08

Researchers at Massachusetts General Hospital (MGH) developed a device that is able to detect and analyze circulating tumor cells (CTCs) in the bloodstream providing information to help oncologists to determine whether the therapy being used works in the patient.

One difficult thing with lung cancer treatment is that the treatment often results in resistance quickly and doctors may not be aware of how effective the treatment he uses in the patient or whether the patient needs a new therapy.

With the new microchip-based device, doctors can monitor genetic changes that occur during therapy and allow them to decide whether a targeted treatment would be appropriate for the patient.

A pilot study of the study will be reported in the July 24, 2008 issue of New England Journal of Medicine.

"The CTC-chip opens up a whole new field of studying tumors in real time," said Daniel Haber, MD, director of the MGH Cancer Center and the study's senior author.

"When the device is ready for larger clinical trials, it should give us new options for measuring treatment response, defining prognostic and predictive measures, and studying the biology of blood-borne metastasis, which is the primary method by which cancer spreads and becomes lethal."

CTCs or circulating tumor cells are living solid-tumor cells and they are found at extremely low levels in the bloodstream. Until the development of the CTC-chip, it has not been possible to get any information of CDCs to help clinicians make a treatment decision.

The device was jointly developed by researchers at the MGH Cancer Center and BioMEMS (BioMicroElectroMechanical Systems) Resource Center.

The current study was meant to test whether the device is capable of helping analyze the genetic mutations that make a tumor sensitive to treatment with targeted therapy drugs.

Early in 2004, researchers at MGH and a team from Dana-Farber Cancer Institute both found that mutations in a protein called EGFR determine whether non-small-cell lung cancer responds to a group of drugs called TKIs including Iressa and Tarceva.

Sensitive tumor cells are responsive to these drugs, but many of them quickly become resistant to the drugs and resume growing.

Among 27 patients who participated in the study, the researchers found 23 had EGFR mutations and 4 did not while CTCs were found in the blood of all patients.

Among the mutation positives, the device detected the primary mutation, which leads to initial tumor development and TKI sensitivity, at a rate of 92 percent based on genetic analysis of CTCs.

Additionally, the CTC-chip also detected a secondary mutation associated with treatment resistance in some patients.

"Patients found to have resistance mutations before treatment probably won't benefit as much or as long from single-agent TKI therapy as those without such baseline mutations," said Lecia Sequist, MD, MPH, of the MGH Cancer Center, a co-lead author of the NEJM paper.

"For those patients we may need to consider other modes of therapy, including combinations+ of targeting agents or second-generation TKIs that can overcome the most common resistance mutation."

The researchers found that in all patients, CTCs dropped quickly after TKI therapy began, but started rising when tumor cells resumed growing. In addition, many mutations occurred during therapy making the treatment difficult.

"The CTC-chip offers the promise of noninvasive continuous monitoring," said Haber.