Keith Stewart, M.B., Ch.B.

Keith Stewart, M.B., Ch.B., conducts translational research in multiple myeloma. This includes both basic and clinical research to identify novel targets for therapy in multiple myeloma.

Dr. Stewart's research is supported by the National Cancer Institute, Multiple Myeloma Research Foundation, and Leukemia & Lymphoma Society, as well as by partnerships with the pharmaceutical industry for clinical trials.

Focus areas

Dr. Stewart's research can be divided into three broad categories:

• Study of the cancer genome. Recently, Dr. Stewart and his colleagues 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 that, when suppressed, sensitize myeloma cells to the effects of chemotherapy. Most recently, they 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. Their first whole human genome sequence was completed in June 2009.

• Cancer drug development. Dr. Stewart and his team have performed high-throughput screens of small molecules to identify inhibitors of myeloma targets. With these screens, they have been successful in identifying a number of small molecules that resulted in cell death when applied to myeloma cells. They have employed a medicinal chemistry approach to the development of analogues for these molecules and will pursue these into preclinical testing and subsequently into clinical trials.

• Clinical trials. These include early investigational phase I studies and large international randomized phase III trials. Novel agents being studied include carfilzomib, pomalidomide, aurora kinase, heat shock protein 90, CDK5 and FGFR3 inhibitors.

Significance to patient care

Dr. Stewart and his colleagues are conducting research that has direct relevance to patient care, as they are discovering markers for prognosis and drug responsiveness, understanding what makes patients resistant to drugs, and applying this knowledge in the clinic with clinical trials exploring novel therapeutics in multiple myeloma, amyloidosis and other blood cancers.