Alternative vascularization mechanisms in cancer: Pathology and therapeutic implications.
Although cancer cells are not generally controlled by normal regulatory mechanisms, tumor growth is highly dependent on the supply of oxygen, nutrients, and host-derived regulators. It is now established that tumor vasculature is not necessarily derived from endothelial cell sprouting; instead, cancer tissue can acquire its vasculature by co-option of pre-existing vessels, intussusceptive microvascular growth, postnatal vasculogenesis, glomeruloid angiogenesis, or vasculogenic mimicry. The best-known molecular pathway driving tumor vascularization is the hypoxia-adaptation mechanism. However, a broad and diverse spectrum of genetic aberrations is associated with the development of the "angiogenic phenotype." Based on this knowledge, novel forms of antivascular modalities have been developed in the past decade. When applying these targeted therapies, the stage of tumor progression, the type of vascularization of the given cancer tissue, and the molecular machinery behind the vascularization process all need to be considered. A further challenge is finding the most appropriate combinations of antivascular therapies and standard radio- and chemotherapies. This review intends to integrate our recent knowledge in this field into a rational strategy that could be the basis for developing effective clinical modalities using antivascular therapy for cancer.
Döme
Balázs
B
Department of Tumor Biology and Thoracic Oncology, National Koranyi Institute of Pulmonology, Budapest, Hungary.
Hendrix
Mary J C
MJ
Paku
Sándor
S
Tóvári
József
J
Tímár
József
J
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003131:Combined Modality Therapy; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000473:pathology
D020533:Angiogenesis Inhibitors