Angiogenesis and anti-angiogenesis in hematological malignancies.
Although it is well established that the growth of solid tumors requires vigorous neovascularization, it has been assumed that leukemias and other hematological malignancies do not depend on angiogenesis. However, the role of angiogenesis in growth and survival of neoplastic cells of the hematopoietic system has recently been recognized, and provides a rationale for novel therapeutic approaches to hematological malignancy. This review summarizes the literature concerning the relationship between angiogenesis and disease progression of several hematological malignancies. It is becoming increasingly evident that agents that interfere with blood vessel formation also block tumor progression, and, accordingly, antiangiogenic therapy has gained much interest as a potential adjunct to conventional therapy of many hematological malignancies. Recent successful applications of antiangiogenic agents that interfere or block the progression of hematological malignancies are evaluated in light of recent demonstrations of potent angiogenic activity of several hematopoietic growth factors. A novel finding regarding the role of angiogenesis in hematological malignancies, which accounts for many clinical observations as well as the apparent independence of these tumors on marrow vascularity, is presented. The information presented in this review will facilitate the design of future clinical trials using antiangiogenic agents for the treatment of hematological malignancies and will provide a basis for the design of experiments undertaken to define the mechanisms involved, mechanisms that may shed new light on the pathology of hematological malignancies.
Ribatti
Domenico
D
Department of Human Anatomy and Histology, University of Bari Medical School, I-70124 Bari, Italy. ribatti@anatomia.uniba.it
Vacca
Angelo
A
Dammacco
Franco
F
English
Denis
D
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002642:Chick Embryo / Q000187:drug effects; D002986:Clinical Trials as Topic; D018450:Disease Progression; D004921:Erythropoietin / Q000627:therapeutic use; D006801:Humans; D007938:Leukemia / Q000473:pathology / Q000628:therapy; D008223:Lymphoma / Q000473:pathology / Q000628:therapy; D020782:Matrix Metalloproteinases / Q000502:physiology; D009369:Neoplasms / Q000628:therapy*; D009389:Neovascularization, Pathologic; D011994:Recombinant Proteins / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D011994:Recombinant Proteins; D004921:Erythropoietin; D020782:Matrix Metalloproteinases