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Localized rectal adenocarcinoma responds well to 5-fluorouracil/radiation-based therapy. Willett et al. present the case of a 55-year-old woman who was diagnosed with extensive and locally invasive carcinoma of the rectum and received bevacizumab in combination with chemoradiotherapy. Upon completion of neoadjuvant therapy, the patient underwent abdominoperineal resection with posterior vaginectomy, hysterectomy and bilateral salpingo-oophorectomy. The authors discuss the complete response seen in this patient and insights into the application and clinical management of using anti-VEGF therapy with chemoradiation.

Bevacizumab with standard chemotherapy improved overall survival in colorectal and lung cancer patients and progression-free survival in breast cancer patients, but this combination failed to increase survival in patients with previously treated and refractory metastatic breast cancer. Reasons for these contrasting results, the mechanisms behind normalization of tumor vasculature for improved drug and oxygen delivery, and the need for biomarkers and imaging techniques to guide patient selection and protocol design are discussed.

Most brain tumors secrete high levels of vascular endothelial growth factor, which can lead to an abnormally permeable tumor vasculature. This hyperpermeability causes vasogenic cerebral edema and increased interstitial fluid pressure, which can prevent adequate penetration of chemotherapy agents to the tumor. This Review focuses on the pathophysiology of vasogenic edema and the potential utility of agents that target angiogenesis, and particularly the vascular endothelial growth factor pathway.

No validated biomarkers currently exist for appropriately selecting cancer patients for antiangiogenic therapy. A number of potential systemic, circulating, tissue and imaging biomarkers have emerged as suitable candidate biomarkers, but all require prospective validation. The authors discuss the current challenges in establishing biomarkers, the advantages and disadvantages of systemic, circulating, tissue and imaging biomarkers, and the future opportunities for validating biomarkers of antiangiogenic therapy.

Hepatocellular carcinoma (HCC) is notoriously resistant to systemic therapies. The success of the anti-VEGF therapy sorafenib in patients with advanced-stage HCC raises hope as well as critical questions on the future development of targeted agents including other antiangiogenic drugs.