Tumor-stromal cell interactions and opportunities for therapeutic intervention.

Tumor tissue is composed of both cancer cells and stromal cells recruited from normal tissue. These cells include fibroblastic cells, endothelial cells, and cells of hematopoietic origin. The host-derived stromal cells play a critical role in all aspects of cancer biology including transformation, progression, tumor growth, and drug resistance. The interactions between stromal cells and cancer cells are of intense interest, and their complex interactions are beginning to be identified. Therapies that target components of the tumor microenvironment are showing efficacy in the clinic, particularly when used in combination with other therapeutic agents. In general these agents have been well tolerated, and targeting the stromal components may be a strategy for circumventing the problem of drug resistance. In this review, we highlight major stromal components, their interactions with tumor cells, and therapeutic approaches that disrupt host–tumor cell interactions. Advances in understanding host stromal components with respect to origin, subsets, and their signaling networks will reveal novel targets. Synergistic approaches that disrupt multiple host–tumor cell signaling pathways will lead to more effective therapies for cancer.