Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy

Abstract

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.

Nanodrug applications in photodynamic therapy

“…Standard PDT can result in hypoxia and other tissue damage, ultimately resulting in inflammation. This can result in the release of angiogenic growth factors (e.g., vascular endothelial growth factor, VEGF) [74]. Therapeutic approaches using anti-VEGF antibody fragments (Lucentis) has given good results for early stages and now combination therapies are under investigation.…”

The characteristics of bone marrow-derived endothelial progenitor cells and their effect on glioma

“…Researchers generally accept that tumors are endowed with angiogenic-inducing capability, and critically dependent on blood vessels for their nutrient and oxygen delivery [6], allowing these cells to grow, invade tissue nearby, spread to the other parts of the body, and form new colonies of cancer cells [7,8], which idea came to light about fifty years ago when Judah Folkman and his group demonstrated that neovascularization is a necessary condition for malignant growth of solid tumors [9]. However, recent studies indicated that bone-marrow-derived cells contributed little to the endothelium of tumor vessels [10].…”

Low-dose metronomic cyclophosphamide treatment mediates ischemia-dependent K-ras mutation in colorectal carcinoma xenografts

“…While moderate inhibition of aberrant growth of the tumor-associated vasculature may in some cases lead to transient improvement of tumor perfusion (Jain, 2005), a more complete therapeutic obliteration of this network implicitly brings about a state of ischemia, which may become lethal to some but not all cancer cells. It follows that such surviving cells may have pre-existing or acquired oncogenic alterations.…”