Massachusetts General Hospital Cancer Center
Charleston, MA

Daniel Haber, M.D., Ph.D
Director, Cancer Center
Massachusetts General Hospital

T.J. Martell Foundation Funded Research at Massachusetts General Hospital Cancer Center

The project supported at the Massachusetts General Hospital Cancer Center by the T.J. Martell Foundation has focused on the application of nanotechnology to personalized cancer medicine. Over the past few years, we have developed, constructed and tested a novel microfluidic chip capable of selecting extraordinarily rare Circulating Tumor Cells (CTCs) from the blood circulation of patients with cancer. This device, which we have called the “CTC-Chip”, consists of a small silicon chamber containing 80,000 columns or microposts, each of which is coated with an antibody that binds tumor cells, but does not attach to normal blood cells. A teaspoon of blood flows through the Chip, resulting in the micropost capture of CTCs, which are present at extremely low concentrations in the blood (1 tumor cell admixed to a billion normal blood cells). Using this technology, we have achieved a 10-20 fold improvement in the isolation and purification of CTCs, compared with currently available approaches. CTCs are particularly important, in that they constitute “metastatic precursors”, cells that are shed by the primary tumor and may lodge in distant organs (lung, brain, bone) causing a cancer to spread and become incurable following surgical resection of the primary tumor. As such, the ability to detect CTCs with high sensitivity may hold the promise of early detection of invasive cancer. In addition, the continuous shedding of CTCs by both primary and metastatic cancers provides a strategy to monitor the genetic state of a cancer as it evolves during therapy. In our first proof of principle study, we demonstrated that CTCs could be used to identify and monitor genetic mutations in lung cancer. Specifically, we were able to identify mutations in the Epidermal Growth Factor Receptor (EGFR) gene in patients with lung cancer who were successfully treated for over a year with targeted inhibitors of the EGFR gene (Iressa or Tarceva). During the past year, we extended our analyses to prostate cancer, demonstrating the presence of PSA-stained cells in the blood of patients with known prostate cancer. We were able to document genetic mutations in prostate cancer CTCs, and demonstrate the disappearance of these cells in the circulation of patients treated with effective hormonal therapy. Of particular interest, we were able to demonstrate the presence of CTCs in a subset of patients with localized prostate cancer before surgical resection. Prostatectomy resulted in an immediate decline in CTCs, confirming the origin of these CTCs from the primary tumor. We are now initiating a large scale clinical trial to determine whether presence of detectable CTCs in patients with apparently localized prostate cancer is evidence of increased vascular invasion by the primary tumor and whether it is correlated with an increased risk of recurrence following surgical resection.  Our CTC project is now focused on further optimization of the technology for clinical applications and studying the biology of cancer metastasis. This project has been funded in part by the T.J. Martell Foundation and we are deeply grateful for this support.