Abstract
New blood vessel formation (angiogenesis) is not only essential for the growth of solid tumors but there is also emerging evidence that progression of hematological malignancies like multiple myeloma, acute leukemias, and myeloproliferative neoplasms, also depends on new blood vessel formation. Anti-angiogenic strategies have become an important therapeutic modality for solid tumors. Several anti-angiogenic agents targeting angiogenesis-related pathways like monoclonal antibodies, receptor tyrosine kinase inhibitors, immunomodulatory drugs, and proteasome inhibitors have been entered clinical trials or have been already approved for the treatment of hematological malignancies as well and in some instances these pathways have emerged as promising therapeutic targets. This review summarizes recent advances in the basic understanding of the role of angiogenesis in hematological malignancies and clinical trials with novel therapeutic approaches targeting angiogenesis.
Highlights
The hypothesis of tumor angiogenesis in malignancies was raised by Judah Folkman: To grow over a certain size of a few millimetres in diameter solid tumors need blood supply from surrounding vessel [ 1]
This review summarizes the role of pathological angiogenesis in hematological malignancies focusing on multiple myelomas (MM), acute leukemias, and myeloproliferative neoplasms (MPN) and its therapeutic intervention with novel agents within clinical trials or already approved
"Angiogenesis switch" in leukemia is documented by increased bone marrow microvessel density (MVD), increased expression of HIF-1, multiple pro-angiogenic factors (VEGF, basic fibroblast growth factor (bFGF), angiopoietin-2), soluble VEGFR, and decreased expression of endogenous angiogenesis inhibitors, such as thrombospondin-1 [ 50, 51]
Summary
The hypothesis of tumor angiogenesis in malignancies was raised by Judah Folkman: To grow over a certain size of a few millimetres in diameter solid tumors need blood supply from surrounding vessel [ 1]. Many studies suggest a role for angiogenesis in the pathogenesis of solid tumors and in hematological malignancies like acute and chronic leukemia, lymphoma, myelodysplastic syndromes, myeloproliferative neoplasms, and multiple myeloma [ 16– 21].
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