Three emerging new drugs for NSCLC: Pemetrexed, bortezomib, and cetuximab

Despite advances made in cytotoxic chemotherapy, the prognosis for patients with non-small cell lung cancer (NSCLC) continues to be poor. New, more effective drugs must be identified and developed to improve the outcome of these patients. Three drugs with promising activity in NSCLC are pemetrexed (Alimta (R); Eli Lilly and Company, Indianapolis, IN, http://www.lilly.com), bortezomib (Velcade (R); Millennium Pharmaceuticals, Inc., Cambridge, MA, http://www.minm.com), and cetuximab (Erbitux (R); ImClone Systems, Inc., New York, NY, http://www.imclone.com). Pemetrexed inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase, enzymes necessary for purine and pyrimidine synthesis, thus causing cell-cycle arrest in the S phase. Bortezomib, a proteasome inhibitor, interferes with the cytosolic protein degradation machinery, namely the ubiquitin-proteasome complex, causing breakdown of cell-cycle regulators and cell-cycle arrest. Cetuximab is a chimeric mouse-human antibody that inhibits ligand-dependent activation of the epidermal growth factor receptor, resulting in receptor internalization and inhibition of downstream pathways that, in turn, causes cell growth and progression. All three drugs are approved for different tumor types, and studies defining their role in NSCLC are under way.