Molecular predictors of response to chemotherapy in lung cancer.
Overall, chemotherapy falls short of the high expectations for improved survival in surgically resected non-small cell lung cancer patients and prolonged survival in the metastatic setting. Conventional chemotherapy trials, even those including new cytotoxic drugs or novel targeting approaches, are hampered by a lack of genetic information. Within the global genomic repair pathway, overexpression of excision repair cross-complementing 1 (ERCC1) has been associated with poor response and survival in cisplatin-treated patients. The lack of DNA adducts in cell nuclei indicates an efficient global genomic repair pathway, which leads to cisplatin resistance. Several xeroderma pigmentosum (XP) genes, including XPD, play an important role in determining the efficiency of the transcription-coupled repair pathway. XPD polymorphism has been related to lower DNA repair capacity and enhanced cisplatin sensitivity. Other DNA repair systems are the base excision repair pathway, in which apurinic/apyrimidinic endonuclease 1 (Ape 1) plays a pivotal role, and the one-step repair pathway, where O(6-)alkylguanine-DNA alkyltransferase (MGMT) has a key function. MGMT methylation can be assessed in serum DNA. By assessing ERCC1 mRNA, cisplatin adducts, XPD polymorphism, Ape 1, and MGMT, we can obtain a complete genetic profile, which can be used in real translational research.
Rosell
Rafael
R
Medical Oncology Service, the Pathology Department, Hospital Germans Trias i Pujol, Insitut Català d'Oncologia, Badalona (Barcelona), Spain.
Taron
Miquel
M
Ariza
Aurelio
A
Barnadas
Agusti
A
Mate
Jose Luis
JL
Reguart
Noemí
N
Margel
Mireia
M
Felip
Enriqueta
E
Méndez
Pedro
P
García-Campelo
Rosario
R
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D004260:DNA Repair / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*
D000970:Antineoplastic Agents; D002945:Cisplatin