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Subspecialties Oncology, Clinical care

Treating Cancer Through Vascular Normalization

For decades, researchers have proposed attacking tumor vasculature to treat a wide variety of solid tumor types with minimal risk to the patient. Although antiangiogenic therapies initially reduce tumor fitness and growth potential by starving cancer cells of oxygen and nutrients, this inhibition is transient and the resulting hypoxia can increase tumor invasiveness and metastatic potential. Could lower-dose treatments that induce vascular normalization offer a solution?

The importance of vasculature for the growth and development of solid tumors has been well established for close to a century. Nonetheless, it was only following Judah Folkman’s 1971 discovery of tumor angiogenic factor that researchers began to explore the therapeutic potential of antiangiogenic strategies (1). Folkman and his colleagues coined the term “antiangiogenesis” and believed that, when this strategy could be clinically achieved, it would be “a powerful adjunct to present methods of cancer therapy.” They theorized that metastases might not arise from a non-vascularized tumor and that such tumors were more vulnerable to chemotherapy and cell-mediated immunologic attack.

Early promise?
The field of angiogenesis progressed (see “Advances in Angiogenesis”) until, in 2004, its theoretical promise became testable with the development of bevacizumab (Avastin), an antibody targeting vascular endothelial growth factor (VEGF) (2). Initially, antiangiogenic agents appeared to deliver on their potential; in the absence of neovascularization, tumors neither grew beyond 2 mm nor underwent metastasis (3). The treatments demonstrated efficacy in many cancer types, including breast, colon, renal, and ovarian – and, in early studies, researchers found no major toxicities (3). In contrast, traditional chemotherapy was characterized by lack of specificity, potential for severe side effects, variable dosing regimens, and development of treatment resistance. As a result, antiangiogenic agents gained appeal and a large number were designed, tested, and made available for clinical use (see Table 1).

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About the Author

Adil Menon

Fourth-year medical student at Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. He is a recipient of the ASCP’s Gold Medical Student Award and holds a Master’s of Bioethics from Harvard Medical School.

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