The focus of our research is to improve the understanding of cancer biology and develop technology that can improve the diagnosis and treatment of cancer.
Cancer is the second largest cause of death and is becoming a larger problem with the aging of the population. Death from cancer is mostly not caused by the loss of function from the site where the tumor arises but caused by dissemination of the disease and destruction of other organs. Cancer cells become dangerous when they break away from the primary site and settle elsewhere in the body. The cascade of events involved in the metastatic process is depicted in the figure 1. Tumor cells dissociate from their surroundings and penetrate through the blood vessel wall to enter into the blood circulation. The majority of tumor cells will be trapped in the capillary beds, die and are then removed by phagocytes.
Occasionally they will adapt to the environment and proliferate. A few tumor cells will penetrate the blood vessel wall to form a metastasis or to stay dormant for an undetermined period of time. Recurrence of cancer may arise after months, years or even decades, this indicates that microscopic disease must have remained present, at least in those patients that relapsed. Knowledge of whether and where “dormant” tumor cells are present and when, why and how they “awaken” is extremely limited.
We pioneered the development of technology that can detect the extremely rare tumor cells in blood of cancer patients. We demonstrated that presence of tumor cells in a tube of blood from patients with metastatic disease is associated with poor survival prospects. The Kaplan Meier Plot in figure 2 shows survival for metastatic prostate cancer patients. The lines show that patients who fall into the bad category after therapy do poorly irrespective of their category before therapy.
People who fall into the good category after therapy do much better regardless of their category before therapy. This shows that treatment effectiveness can be measured an amazing two months earlier than conventional imaging techniques. Imagine what can be done for a patient in two months!
Next, the question arises which therapy can be effective. To that end our group is exploring means to assess the presence of treatment targets at the protein and gene level on tumor cells. Here, the technological challenge is to determine as many targets as possible on the same few cells.
Tumor cells can not only be detected in blood of patients with metastatic disease, but also in patients who are clinically free of disease, albeit at lower frequency. Cancer cells detected in blood of these patients clearly behave differently than the ones detected in patients with metastatic disease. Understanding the differences between these “killer” and “dormant” tumor cells may hold the key to our understanding of metastasis. The technology to detect disseminated tumor cells in a patient’s body and to examine their make-up needs to be improved for further exploration of this question. We may also need the development of in-vivo-cytometry technology. Proof of the presence of dormant tumor cells and understanding of the mechanisms involved in maintaining their dormancy status, will ultimately lead to controlling cancer.