Circulating prostate tumour cells and Micro Electronic Machines
Tuesday, 2 December 2008 - At the Prostate Cancef Foundation (PCF) 15th Annual Scientific Retreat held at Incline Village, Nevada, USA, Dr. Daniel Haver and Mehmet Toner of the Massachusetts General Hospital Cancer Center discussed new approaches to detecting circulating tumour cells.
Haber and Toner have developed a novel microfluidic microelectromechanical systems (MEMS) device that enables a simple blood test to detect and characterize the circulating tumour cells (CTCs) responsible for metastasis.
Although it is not yet approved for clinical use, the MEMS device may eventually play a key role in numerous aspects of cancer diagnosis and treatment, including detecting and evaluating metastatic disease, selecting and individualising initial surgical and medical therapies, monitoring disease progression, detecting the occurrence of therapy-induced mutations and the consequent development of resistance, and understanding the fundamental biology of metastasis.
Among the conclusions presented by Haber were:
- Microfluidic MEMS (Micro Electronic Machines) is a breakthrough technologyfor circulating tumor cell (CTC) isolation and characterisation.
• Presence of CTCs in numbers higher than suspected across multiple tumour types.
- In lung cancer, this test provides a non-invasive serial monitoring for response and molecular mechanisms of resistance.
- In prostate cancer, it has potential applications for analysis of "localised" disease and disease progression.
Current detection methods successfully detect CTCs in only half of samples known to contain them. The new device consists of approximately 80,000 micro posts covered with antibodies against the epithelial cell adhesion molecule (EpCAM), permitting them to selectively bind CTCs.
The bound cells are visualised with fluorescent staining and optical microscopy. The device has been used to detect CTCs from prostate, lung, breast and gastrointestinal cancers. Staining techniques for specific molecules, such as prostate specific antigen (PSA), provide reliable confirmation of the source of the CTC.
The PCF is funding the next phase of research being conducted with the MEMS device developed Drs. Haber and Toner. Using the device, Drs. Rick Lee and Matthew Smith at the Massachusetts General Hospital Cancer Center are directing clinical trials to analyse CTCs in prostate cancer patients.
The research seeks to validate prostate cancer applications for CTC analysis similar to those already shown for lung cancer. The clinical trials include correlating CTCs with borderline or rising PSA levels, pathological and histological analysis, and the likelihood of post-operative recurrence; rapidly measuring therapeutic responses; detecting the development of resistance and genetic changes, such as translocation and androgen receptor mutation; and understanding the disease process to identify diagnostic markers and novel therapeutic targets.
This technology provides a minimally invasive technique for early detection of tumours and metastasis. A single cancer cells can be isolated from over a billion red blood cells in a routine blood test using this new convergence of microelectronics, material sciences, and molecular biology. At the Prostate Cancer Foundation this approach is called a "liquid biopsy" for progression biomarkers.
The PCF said there is an enormous amount to learn about the strengths and limitations of these liquid biopsies and how to apply them to routine daily care of patients. Analysis of CTCs can indicate the type of cancer, its aggressiveness, and its susceptibility to particular treatments.
New biotechnologies allow a single isolated tumour cell in a patient to be analyzed for genes that can help predict response to drugs before they are used. Also, it may be possible to measure remissions earlier using liquid biopsies that using conventional CT scans and other radiology tests.
Although the absolute number of CTCs in the blood did not correlate to tumour size, variations in CTC levels over the course of treatment do correlate with X-Ray evaluations of progression and remission, providing an important and responsive means of monitoring the efficacy of standard or experimental regimens.
Source: Prostate Cancer Foundation, USA.