title: Pharmacogenomics in non-small-cell lung cancer chemotherapy.
abstract: The disappointing results in long-term survival of patients who have a resectable non-small cell lung cancer (NSCLC) may reflect the lack of knowledge on the way by which molecular abnormalities in neoplastic cells affect responsiveness to adjuvant therapy. This issue deserves intensive investigation to select methodological approaches for a new generation of chemotherapeutic strategies. Remarkable advances in the understanding of NSCLC biology have been made, including the discovery of critical mutations in oncogenes (i.e. K-Ras and c-myc), as well as the loss of tumor-suppressor genes, such as TP53, p16(INK4) or Rb. Other studies demonstrated the role of mutations or deregulation of the expression of several molecular determinants involved in cell cycle control such as epidermal growth factor receptor (EGFR). All these characteristics, as well as alterations in gene products directly related to drug activity, might contribute to the aggressive behaviour of NSCLC. The future challenge of chemotherapy of NSCLC relies on the identification of molecular markers that are predictive of drug sensitivity and are helpful in the selection of chemotherapeutic agents best suited to the individual patient. Other intriguing issues will be the identification of the optimal drug sequence in combination regimens and the pharmacogenetics of severe toxicities. Moreover, due to the developments of novel technologies to decipher genetic alterations involved in tumor progression, new agents are gaining momentum, including inhibitors of intracellular signal transduction, and a large body of research, using prospective clinical trials, should be devoted to this area.
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Internal Medicine, University of Pisa, Pisa, Italy. r.danesi@med.unipi.it
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pasqualetti
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Crea
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Altavilla
authors.forename: Mario
authors.initials: M
authors.lastname: Del Tacca
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000187:drug effects; D010597:Pharmacogenetics
chemical_list: D000970:Antineoplastic Agents