Last Updated: 04/06/07
Normalization of Tumor Vasculature
Because cancer cells in solid tumors require access to blood vessels for growth and metastasis, inhibiting vessel formation through a process called antiangiogenesis offers hope for reducing the mortality and morbidity from these tumors. However, when administered as single agents, antiangiogenic drugs have produced only modest objective responses in clinical trials, and overall, they have not yielded significant long-term survival benefits. In contrast, when given in combination with chemotherapy, bevacizumab, an antibody targeted against the potent angiogenic molecule vascular endothelial growth factor (VEGF), has produced an unprecedented five-month increase in survival in colorectal cancer patients.
Work by Dr. Rakesh Jain of Massachusetts General Hospital, supported with NCI funding managed by RRP, has led to a better understanding of the molecular and cellular underpinnings of vascular normalization. This research suggests that certain antiangiogenic agents improve delivery of drugs and oxygen to the targeted cancer cells by transiently improving blood flow to tumors. The increased drug penetration to the tumor can enhance the outcome of chemotherapy, and increased levels of oxygen can enhance the efficacy of radiation therapy and many chemotherapeutic agents. This work may ultimately lead to more effective therapies, not only for cancer but also for other diseases with abnormal vasculature, as well as regenerative medicine, in which the goal is to create and maintain a functionally normal vasculature.
Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005:307;58–62.
