New targets for non-small-cell lung cancer therapy

Lung cancer remains the leading cause of malignancy-related deaths in the USA, regardless of advances in therapeutic agents. Non-small-cell lung cancer demonstrates great molecular heterogeneity in which several pathways are simultaneously active leading to tumorigenesis. Novel agents targeting specific pathways associated with apoptosis, cell proliferation, angiogenesis and other mechanisms have emerged as a separate and unique therapeutic class delivering promising results in a vast number of malignancies. This innovative class of agents has been studied in advanced-stage non-small-cell lung cancer and, although some agents have demonstrated a clinical benefit, the overall course of the disease remains relatively unchanged, still holding a poor overall prognosis. Most of these agents have been shown to be 'cytostatic', inducing more stable disease rather than objective responses. Thus, the entrance of these novel agents into our drug armamentarium seems to be more attractive in combination with conventional chemotherapy agents based on additive or synergistic response seen with this combined approach. Herein, we review the most relevant clinical data using these novel targeted agents either alone or in combination with chemotherapy in non-small-cell lung cancer.