Molecular markers and targeted therapy with novel agents: prospects in the treatment of non-small cell lung cancer.
Detection of genomic differences predictive of drug response or resistance in individual patients may allow therapy to be customized to the characteristics of particular tumors. Preliminary findings are that non-small cell lung cancer patients overexpressing ERCC1 mRNA have lower response to cisplatin chemotherapy, while those overexpressing ribonucleotide reductase mRNA have limited benefit from gemcitabine. In addition, overexpression of beta-tubulin III and stathmin can influence the sensitivity to microtubule interacting drugs, like vinorelbine and paclitaxel. The introduction of biological agents which target highly specific intracellular pathways offers the promise of enhancing the efficacy of cytotoxic chemotherapy. Among many promising biological agents is the monoclonal antibody C225, which blocks the EGFR receptor. The addition of C225 appears to induce responses in a proportion of colon cancer patients refractory to 5-FU or irinotecan, supporting pre-clinical evidence of synergistic activity. It also appears from xenograft data that C225 enhances the sensitivity of tumors to radiation and docetaxel or the combination.
Rosell
Rafael
R
Hospital Germans Trias i Pujol, Medical Oncology Service, Ctra Canyet, s/n 08916 Badalona, Barcelona, Spain. rrosell@ns.hugtip.scs.es
Fossella
Frank
F
Milas
Luka
L
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D000068818:Cetuximab; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004720:Endonucleases; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011237:Predictive Value of Tests; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis; D018714:Radiotherapy, Adjuvant; D012264:Ribonucleotide Reductases / Q000032:analysis / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015415:Biomarkers; D004268:DNA-Binding Proteins; D011506:Proteins; D000077146:Irinotecan; D012264:Ribonucleotide Reductases; D066246:ErbB Receptors; C071447:ERCC1 protein, human; D004720:Endonucleases; D000068818:Cetuximab; D002166:Camptothecin