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H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, USA
by Lynne Lederman, PhD
Myeloma cell lines have been used for testing drug resistance, but one major obstacle is that these myeloma cell in patients grow in the bone marrow microenvironment, not in isolation as cell lines do in culture. One of Dr. Dalton’s working hypotheses is that the bone marrow microenvironment creates a sanctuary for tumor cells and protects them against insults, including radiation, drugs, and biologics. The aim of therapy should be not only to reduce the tumor burden and eliminate residual disease, but also to prevent the bone marrow microenvironment from helping drug resistance to develop. The interaction of myeloma cells with the bone marrow microenvironment can be divided into two categories: 1) physical contact involving cell adhesion molecules and their ligands, and 2) soluble factors, e.g., IL-6. One approach to study these interactions is to isolate factors and ligands, determine how they are affected by various therapeutics, then add them back into the system to assess their effect. Gene expression profiling (GEP) and other techniques also be used to identify important factors in drug resistance. Once factors are identified, strategies to block them can be developed. One approach has been to use the decapeptide HYD1 to block cell adhesion-mediated drug resistance mediated by beta-1-integrin activity.