C. Anthony Blau, MD
Professor and Co-Director, Institute for Stem Cell and Regenerative Medicine
We are establishing the infrastructure to treat a small number of highly motivated cancer patients as individual experiments: in scientific parlance, an "N of 1." Vast amounts of data will be analyzed from each patient's tumor to predict which proteins should be targeted in order to destroy the cancer. Each patient would then receive a drug regimen tailored to his or her tumor. In this kind of single-subject approach, there is no control group against which to compare the response of the experimental subject. Instead, each patient would serve as his or her own control, using a technique called serial molecular monitoring. In this technique, the patient would receive a drug designed to block a particular target protein. A biopsy would then be performed to confirm whether the drug had worked and the target had indeed been blocked. In this way, researchers would track the tumor's molecular response to treatment through repeated biopsies (a requirement that may eventually be replaced by sampling blood). One of the most important advantages of serial molecular monitoring is that it would reveal strategies that tumors adopt to evade therapy, possibly uncovering new targets of opportunity.
This patient-centered approach represents a dramatic departure from traditional oncology. Because these novel patient-specific combinations of drugs could have unforeseen side effects, the methodological, regulatory, and ethical framework for cancer research would need to be reconsidered from the ground up. Therapies that appear to be effective would be validated in small trials involving other patients with similar molecular profiles. Unsuccessful therapies could be analyzed to refine our understanding of tumor biology and drug mechanisms. The N of 1 approach may not hit immediate home runs. However, the extensive body of knowledge generated from each patient should, upon aggregation with data from other patients, enable us to tell from a blood sample which patients will respond to particular drugs. In time, we hope to be able to stop tumors by anticipating the escape routes they are likely to take.
In addition, we are developing a new generation of cell therapies that involves placing cells under the "remote control" of small molecule drugs. Over the past decade we have completed much of the ground-work establishing the feasibility of this approach. We believe that the approaches we are developing today will be commonplace 100 years from now (see the last chapter of "Thomas' Hematopoietic Cell Transplantation," written by Ernie Beutler), but we are most interested in pursuing approaches with (hopefully) nearer-term clinical applications.