By necessity, this article focuses on only a handful of molecules with demonstrated ability to affect growth of myeloma cells. The heterogeneity in growth-factor responsiveness has made formulation of a uniform hypothesis a daunting challenge. One trait that appears to be consistent among all myeloma patients is the uncoupling of the normally highly integrated relationship between terminal differentiation and loss of growth potential. Thus, the common feature in myeloma may not be the precise cytokines or cell-to-cell interactions that drive tumor-cell growth, but rather the underlying genetic traits that afford the tumor cell the ability to proliferate despite its relatively advanced stage of differentiation. The success of current strategies used to treat myeloma patients has thus far been somewhat limited, and in general, has only modestly prolonged survival. It is clear that successful treatment of this disease will require the development of new therapeutic agents aimed at the biochemical events that sustain the aberrant growth of the tumor cells. The knowledge of cell signaling, gene transcription, and cell growth and differentiation has expanded rapidly, and this information has provided a greater understanding of the cell biology of a variety of malignancies. Application of this information to the study of multiple myeloma, however, has thus far been relatively limited, primarily because the heterogeneity of the disease and the lack of appropriate model systems. Review of the literature, particularly over the last 5 years, reveals a significant number of exciting new findings in this field and the development of new model systems that are certain to yield greater insight into this devastating disease.
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