Role of myeloid cells in vascular endothelial growth factor-independent tumor angiogenesis

PURPOSE OF REVIEW: Targeting the vascular endothelial growth factor (VEGF) pathway has had a significant impact in the therapy of cancer and intraocular neovascular disorders. Similar to other therapies, inherent/acquired resistance to anti-VEGF drugs may occur in cancer patients, leading to disease recurrence. This review describes recent findings on the role of myeloid cells in refractoriness or/and acquired resistance to such therapies. RECENT FINDINGS: Various myeloid cell types, including tumor-associated macrophages, Tie2-expressing monocytes and neutrophils, have been implicated in tumor angiogenesis. Several cytokines involved in the mobilization and/or proangiogenic effects of these cells represent therapeutic targets. CD11b+Gr1+ myeloid cells have been shown to render tumors refractory to angiogenic blockade by VEGF antibodies. This effect was mediated by the secreted protein Bv8, which is upregulated by granulocyte colony-stimulating factor. SUMMARY: Progress in unraveling proangiogenic mechanisms dependent on various myeloid cell types has expanded our understanding of tumor angiogenesis and has generated a number of potential therapeutic targets.