Myeloma Today: Prof. Van Ness, please tell us a little about your background.
Prof. Van Ness: I hold a Ph.D. in Biochemistry from the University of Minnesota. I did my post-doctoral work at Fox Chase Cancer Center in Philadelphia and was Assistant Professor at the University of Iowa from 1982 to 1987. Currently, I am Professor and Head of the Department of Genetics, Cell Biology and Development, at the University of Minnesota and Director of Cancer Genetics for our NCI designated Cancer Center Laboratory. I am the co-chair of the Eastern Cooperative Oncology Group (ECOG) Myeloma Committee.
MT: How did you become interested in genetics?
Prof. Van Ness: As a graduate student, I had a basic interest in molecular biology and
immunology, and did post-doctoral work studying immunoglobulin gene regulation. My faculty career was primarily aimed at extending studies of molecular immunology using mouse models. When I moved to Minnesota to join the Institute of Human Genetics in 1987, I expanded our studies to human, using lymphoid tumor models to study antibody gene regulation. Shortly after I got to Minnesota, I was approached by Dr. Martin Oken and asked if I had any
interest in getting involved in human studies of myeloma. Dr. Oken enlisted my
participation in the Myeloma Committee of the Eastern Cooperative Oncology Group
(ECOG) where I began examining antibody genes as clonal markers for the
disease. Having access to clinical samples sparked an interest in studying some of the genetics and signaling events in disease initiation, progression and therapeutic response. My collaborations with Dr. Robert Kyle and colleagues at the Mayo Clinic provided further interactions that were important in establishing a research program in myeloma.
MT: In your opinion, what are the most important areas of research to better understand myeloma?
Prof. Van Ness: Because of the large heterogeneity we see in myeloma disease progression and response, I believe this is a reflection of significant genetic heterogeneity. Indeed, we know there are subsets of myeloma that have specific oncogene, or tumor suppressor gene mutations, as well as a variety of chromosomal abnormalities. In addition, the bone marrow microenvironment likely has a major contribution to disease progression and response. As a result, gene expression patterns as well as intracellular signaling pathways are altered. New technical advances now provide some exciting approaches to examine how these alterations influence disease initiation, progression and response.
MT: Which types of genetic studies are most important?
Prof. Van Ness: First, it is important to identify key genetic events that contribute to the initiation of the disease. Second, the altered expression patterns identified will allow us to better classify and predict disease progression. Third, identification of altered genetic expression and critical signaling pathways will offer identification of new therapeutic targets. The new directions in cancer genetics are to develop more patient specific characterization and therapeutic approaches. There is a lot of excitement in the development of large genetic profiles that can be correlated to clinical profiles and their use in designing patient specific therapeutic approaches.
MT: Do you think that human genome mapping will make a quantum difference in
the field of myeloma?
Prof. Van Ness: Genome mapping is just the beginning of an enormous amount of data that will be soon coming. While genome projects may identify chromosomal or genetic loci, it is the functional genomic studies that will put gene action into the
appropriate perspective to have an impact on understanding this disease. Since gene expression ultimately influences protein
production and function, the integration with new proteomic advances will be critical. Pharmaceutical applications will define pharmacogenetics, whereby real therapeutic applications will come from the genomic and proteomic research. One of the major challenges will be handling the large data output, and expertise in bioinformatics, data management, and analysis is key.
MT: What would be the time scale between analyzing the new DNA information as
it relates to myeloma and developing and implementing new treatment strategies?
Prof. Van Ness: Genetic profiling is happening now, although data analysis is a major hurdle to overcome. How does one integrate all the genetic analysis data into meaningful clinical predictions or strategies? Exciting new discoveries in genetic patterns and signaling will likely continue for the next several years. Better predictors of clinical response may come first, followed by new pharmacologic targets within the next five years. This will be a true test for the future
power of genetics – to make a real impact on therapy that can yield effective therapeutic strategies within the next five years.
MT: Where do you see most of this work occuring? Pharmaceutical companies? NCI-supported cooperative groups? Individual research teams?
Prof. Van Ness: Individual research laboratories are making major technical advances in developing genetic profiles. The NCI supported cooperative groups need to get
into the process because they have access to large clinical studies, with clinical data bases to which the genetic studies will be correlated and genetic predictors tested. There also needs to be coordination through consortiums of genetic researchers who use and have access to common genetic tools (e.g. an agreement for common use of a myeloma relevant gene microarray). Bioinformatics and people with expertise in developing novel analytical approaches are critical. Partnerships with pharmaceutical companies with these clinical and research groups will provide opportunities for new agents and effective treatment development. These new strategies then come full circle with clinical trials through the cooperative groups.
MT: What do you see as the role of the IMF in this process?
Prof. Van Ness: First, the IMF has played a very important role in funding new research initiatives. This type of funding is tremendously important to seed new approaches, and generate results that can be used to springboard to nationally funded grants. The IMF’s encouragement of both new investigators through its fellowship program and senior awards have filled an important gap in research funding opportunities. Secondly, IMF can effectively develop an organization and cooperation in research efforts because of its network of both patients and researchers. IMF can play an important role in directing national awareness of the public and government agencies to give this disease much needed attention.