New oral multitargeted antiangiogenics in non-small-cell lung cancer treatment.

Non-small-cell lung cancer is a particularly aggressive cancer. Combination chemotherapy remains the standard therapy for patients with advanced or metastatic disease. However, despite the available treatment options for patients who progress beyond first-line therapy, prognosis remains poor. Angiogenesis is a tightly regulated process controlled by a delicate balance between pro- and antiangiogenic factors and their receptors; tumors induce angiogenesis by disrupting this balance and secreting various growth factors. Inhibition of tumor-related angiogenesis has become an attractive target for anticancer therapy. Antiangiogenic strategy includes monoclonal antibodies against VEGF and VEGF receptor and small molecule inhibitors of VEGF tyrosine kinase activity (tyrosine kinase inhibitors). Tyrosine kinase inhibitors are orally active, small molecules that represent a new class of drugs with a relatively high safety profile. They are targeted therapies that play their anticancer role interfering with specific cell signaling. This review focuses on such oral antiangiogenic agents that have been approved and are in advanced clinical development for the treatment of patients with advanced non-small-cell lung cancer.