Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy.
Solid tumors require blood vessels for growth, and many new cancer therapies are directed against the tumor vasculature. The widely held view is that these antiangiogenic therapies should destroy the tumor vasculature, thereby depriving the tumor of oxygen and nutrients. Here, I review emerging evidence supporting an alternative hypothesis-that certain antiangiogenic agents can also transiently "normalize" the abnormal structure and function of tumor vasculature to make it more efficient for oxygen and drug delivery. Drugs that induce vascular normalization can alleviate hypoxia and increase the efficacy of conventional therapies if both are carefully scheduled. A better understanding of the molecular and cellular underpinnings of vascular normalization may ultimately lead to more effective therapies not only for cancer but also for diseases with abnormal vasculature, as well as regenerative medicine, in which the goal is to create and maintain a functionally normal vasculature.
Jain
Rakesh K
RK
E. L. Steele Lab for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, and Harvard Medical School, Cox-7, 100 Blossom Street, Boston, MA 02114, USA. jain@steele.mgh.harvard.edu.
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015687:Cell Hypoxia; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D009389:Neovascularization, Pathologic; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A