Tumor-associated neovasculature is a critical therapeutic target; however, despite significant progress made in the clinical efficacy of anti-vessel drugs, the effect of these agents remains transient: over time, most patients develop resistance, which inevitably leads to
tumor progression. To develop more effective treatments, it is imperative that we better understand the mechanisms involved in
tumor vessel formation, how they participate to the
tumor progression and
metastasis, and the best way to target them. Several mechanisms contribute to the formation of
tumor-associated vasculature: i) neoangiogenesis; ii) vascular co-option; iii) mosaicism; iv) vasculogenic mimicry, and v) postnatal vasculogenesis. These mechanisms can also play a role in the development of resistance to
anti-angiogenic drugs, and could serve as targets for designing new anti-vascular molecules to treat solid as well as
hematological malignancies. Bone marrow-derived endothelial progenitor cell (
EPC)-mediated vasculogenesis represents an important new target, especially at the early stage of
tumor growth (when EPCs are critical for promoting the "angiogenic switch"), and during
metastasis, when EPCs promote the transition from micro- to macro-
metastases. In
hematologic malignancies, the
EPC population could be related to the neoplastic clone, and both may share a common ontogeny. Thus, characterization of
tumor-associated EPCs in
blood cancers may provide clues for more specific anti-vascular
therapy that has both direct and indirect anti-
tumor effects. Here, we review the role of vasculogenesis, mediated by bone marrow-derived EPCs, in the progression of
cancer, with a particular focus on the role of these cells in promoting progression of
hematological malignancies.