Device could continuously monitor tumour's genetic makeup
A device developed at the Massachusetts General Hospital (MGH) could help scientists to analyse cancer cells circulating in the bloodstream so that they can determine the genetic makeup of a person's tumour and monitor any mutations that occur during treatment.
The CTC-chip detects circulating tumour cells (CTCs) - cancer cells that are found in tiny amounts in the bloodstream - and analyses the genetic makeup of the cells, thus identifying mutations that can make a tumour sensitive or resistant to certain drugs.
Senior author Dr Daniel Haber, director of the MGH Cancer Centre and professor of medicine at Harvard Medical School, said that the CTC-chip "opens up a whole new field of studying tumours in real time".
"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."
The researchers carried out a trial in which they used the device to analyse blood samples from 27 patients with non-small-cell lung cancer (NSCLC).
The team had previously discovered that mutations in a protein called EGFR determine whether NSCLC tumours will respond to drugs called Tyrosine Kinase Inhibitors (TKIs) (such as Iressa and Tarceva).
A research report in the New England Journal of Medicine reveals that the CTC-chip detected CTCs in samples from all 27 patients.
Twenty-three of the patients had EGFR mutations and the CTC-chip correctly identified these mutations 92 per cent of the time, as well as a secondary mutation associated with resistance to treatment in some patients.
Co-author Dr Lecia Sequist, also of the MGH Cancer Centre, commented: "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.
"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."
One of the most important aspects of the CTC-chip is that it could enable scientists to monitor genetic mutations in tumours during the course of treatment.
The researchers took blood samples at regular intervals during four patients' treatments and found that levels of CTCs dropped sharply after TKI treatment began and then started to rise again after the patients' tumours started to re-grow.
The team noticed that the tumours' genetic makeup continued to evolve throughout the course of treatment, with a common resistance mutation appearing that was not present at the start of treatment.
Dr Haber noted: "It's essential to know exactly what you're treating at the time you are treating it.
"Biopsy samples taken at the time of diagnosis can never tell us about changes emerging during therapy or genotypic differences that may occur in different sites of the original tumour, but the CTC-chip offers the promise of non-invasive continuous monitoring."