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; Eli Lilly and Company, Indianapolis, IN, http://www.lilly.com), bortezomib (Velcade; Millennium Pharmaceuticals, Inc., Cambridge, MA, http://www.mlnm.com), and cetuximab (Erbitux; 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.
Dubey
Sarita
S
University of Wisconsin Comprehensive Cancer Center, 600 Highland Avenue, Madison, Wisconsin 53792, USA.
Schiller
Joan H
JH
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000068818:Cetuximab; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008495:Medical Oncology / Q000639:trends; D000068437:Pemetrexed; D011719:Pyrazines / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D001897:Boronic Acids; D005971:Glutamates; D011719:Pyrazines; D000068437:Pemetrexed; D006147:Guanine; D000069286:Bortezomib; D000068818:Cetuximab