Drug resistance and drug development in multiple myeloma.

Circumvention of drug resistance in multiple myeloma is a major obstacle to improving clinical outcomes for myeloma patients. Identification of several mechanisms of acquired drug resistance has led to the development of chemosensitizing agents that counter specific drug resistance mechanisms. Initial successes in therapy using chemosensitizers often culminate in relapse because of the multifactorial nature of acquired multidrug resistance. Therefore, it may be important to design therapeutic strategies that focus on mechanisms that allow for cell survival following initial treatments, before the acquisition of multidrug resistance. It has been proposed that extracellular effectors such as cytokines, matrix components, and adjacent cells may provide a sanctuary for cancer cells by preventing stress-induced cell death. This review focuses on research implicating the cancer cell environment as a particularly important determinant in the emergence of drug resistance. Copyright 2002, Elsevier Science (USA). All rights reserved.