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Abstract
Bcr-abl kinase inhibitors have provided proof of principal that targeted therapy holds
great promise for the treatment of cancer. However, despite the success of these agents
in treating chronic myelogenous leukemia (CML), the majority of patients continue
to present with minimal residual disease contained within the bone marrow microenvironment.
These clinical observations suggest that the bone marrow microenvironment may provide
survival signals that contribute to the failure to eliminate minimal residual disease.
The bone marrow microenvironment is comprised of multiple sub-domains which vary in
cellular composition and gradients of soluble factors and matrix composition. Experimental
evidence indicate that exposure of tumor cells to either bone marrow derived soluble
factors or the extracellular matrix can confer a multi-drug resistance phenotype.
Together, these data indicate that targeting such pathways may be a viable approach
for increasing the efficacy of chemotherapy. Moreover, we propose that personalized
medicine must go beyond understanding predictive models inherent to tumors but rather
build predictive models that consider diversity in response due to interactions with
the tumor microenvironment. Although review will focus on CML, understanding the contribution
of the bone marrow microenvironment could contribute to rationale combination therapy
in other types of leukemia, multiple myeloma and solid tumors which metastasize to
the bone.
Copyright 2010 Elsevier Inc. All rights reserved.