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The cyclic administration of conventional (i.e., maximum -tolerated dose [MTD]) chemotherapy targets primarily the tumor cell population. In contrast, chemotherapeutics used at lower doses but on a more frequent basis, and without treatment-free breaks, preferentially affect the tumor vasculature. This so-called low-dose metronomic (LDM) form of chemotherapy administration can be considered as a complementary and/or alternative form of antiangiogenic therapy to the use of targeted antiangiogenic agents such as antibodies or small molecule drugs that interfere with vascular endothelial growth factor (VEGF) pathways. However, it becomes increasingly clear that LDM chemotherapy affects also aspects of the tumor microenvironment other than angiogenesis such as immune responses. Herein, we summarize the complex effects of LDM chemotherapy on the tumor microenvironment, with special emphasis on angiogenesis. We also compare the effects of LDM versus MTD chemotherapy. Finally, we outline how pharmacogenetic characteristics of the tumor host and microenvironment may be exploited in the future to predict response to LDM therapy. [ABSTRACT FROM AUTHOR]

Targeting angiogenesis is an evolving field of cancer research. Tumor angiogenesis is considered as an important step in the progression and metastasis of prostate cancer. Several pathways that converge toward promotion of growth, proliferation, and survival of prostate cancer cells have been targeted, including modulation of proangiogenic factors such as vascular endothelial growth factor (VEGF), tyrosine kinases, cytokines, and the extracellular matrix. Accurately measuring antitumor activity remains a challenge with the use of investigational angiogenesis inhibitors in prostate cancer. [ABSTRACT FROM AUTHOR]