Translational Research in Multiple Myeloma:

Dr. Stewart has both basic and clinical research interests in identifying novel targets for therapy in multiple myeloma. His research is supported by the National Cancer Institute, Multiple Myeloma Research Foundation, Leukemia & Lymphoma Society, and by partnerships with the pharmaceutical industry for clinical trials. The research programs can be divided into three broad categories:

Study of the Cancer Genome
Recently we have focused on the use of high throughput druggable genome RNAi screening in the presence or absence of therapeutic agents such as bortezomib and lenalidomide. This work will lead to the identification of targets which when suppressed sensitize patients' myeloma cells to the effects of chemotherapy. Most recently we have also begun whole genome sequencing of myeloma cells in patients who have become resistant to chemotherapy drugs in an attempt to identify mechanisms of resistance. Our first whole human genome sequence was completed in June of 2009 in collaboration with colleagues at TGen.

Cancer Drug Development
We have performed high throughput screens of small molecules to identify inhibitors of the cyclin D pathway, which unifies all myeloma tumors. We have been successful in these screens in identifying a number of small molecules which, when applied to myeloma cells, resulted in cell death consequent to the inhibition of cyclin D. We have employed a medicinal chemistry approach to the development of analogues for these molecules and will pursue these into preclinical testing and subsequently clinical trials. These molecules include Kinetin Riboside and Pristimerin, as was recently published by our group. In addition to the medicinal chemistry approach, we have also begun development of inhibitors of a novel kinase identified through our RNAi screening. This kinase inhibitor should result in broad death of myeloma cells in many patients and it is our ultimate goal to bring this to clinical trials.

Clinical Trials
Dr. Stewart is lead investigator on numerous clinical trials, including early investigational phase 1 studies and large international randomized phase 3 trials. Novel agents being studied include: Carfilzomib; Pomalidomide; Aurora Kinase, Heat Shock Protein 90; CDK5 and MCL1 inhibitors.