Targeting the Tumor Stroma in Breast Cancer

Tumor stroma is constituted by blood vessels, fibroblasts, leukocytes, and intercellular fibers. As opposed to the stroma of normal tissue, tumor stroma has an aberrant physiology. The tumor cells can secrete growth factors that can reprogram the stroma so that it exerts several tumor progression roles and supports a positive feedback loop that preserve a microenvironment favorable for the tumor and hostile for the patient’s interests (limiting the delivery of chemotherapy, blocking immune response, and keeping hypoxic conditions). In this review, we discuss the recent advances in understanding this tumor-stromal cross-talk and how the signaling systems implicated on it can be useful for targeted therapeutics. We will discuss the available results from trials completed with targeted agents with antistromal effects and also retrospective studies conducted with patient cohorts taking other non-cancer drugs to which recently several antistromal properties have been described, such as antihypertensives. Finally, we will show our preclinical results regarding hypoxia tracking with 18F-fluoromisonidazole, a PET tracer, as a potential tool to specifically monitor the positive or negative effects of antistromal agents. © 2015, Springer Science+Business Media New York.