THURSDAY JULY 3, 2008 (foodconsumer.org) -- 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.
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