VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF)

VEGF (vascular endothelial growth factor) is a protein that promotes the growth of new blood vessels, a process known as angiogenesis. Because growing tumors require an increase in blood supply to survive, they often express high levels of VEGF. VEGF initiates angiogenesis by interacting with a protein receptor known as VEGFR (vascular endothelial growth factor receptor), which sends a signal to the cell to initiate angiogenesis.

Biomarkers

Biomarkers that would help predict tumor response to targeted therapy with anti-VEGF drugs are currently under investigation. The markers ICAM and E-selectin, as well as VEGF itself, have all been examined, but none appears to be especially predictive (17).

Targeted Therapy

Several different types of drugs have been developed to block angiogenesis by targeting either VEGF or VEGFR.

Avastin (bevacizumab)

Avastin (bevacizumab), a monoclonal antibody that binds to and inactivates VEGF, is the only molecular targeted drug currently approved for first-line treatment of NSCLC (33). Avastin is used in combination with traditional cytotoxic chemotherapy. Several studies have reported a significant advantage for NSCLC patients treated with Avastin in combination with chemotherapy compared to patients treated with chemotherapy alone (51). Clinical trials refining the ideal dosage and chemotherapy combinations for Avastin in NSCLC are ongoing.

Due to high levels of toxicity, Avastin is not recommended for use in patients who are elderly or who have brain metastases. However, Avastin is currently being tested in combination with Tarceva for patients whose brain metastases have been treated.

Avastin is also indicated for the treatment of metastatic colorectal cancer and breast cancer and is currently being evaluated in additional cancer types, including renal cell carcinoma, ovarian cancer, and pancreatic cancer. Avastin has been extremely successful in treating metastatic colorectal cancer: recent studies have shown that Avastin increases the length of time before disease progression for patients in various risk groups and can also extend lifespan even when administered after disease progression (49, 50).

Other drugs

Several small molecule drugs that target VEGFR -- sorafenib, sunitinib, vandetanib (ZD6474), and cediranib -- are currently being evaluated for efficacy and toxicity in clinical trials for treatment of NSCLC. These drugs are known as multi-target inhibitors because they inhibit other receptors (including EGFR and PDGFR) in addition to VEGFR.