title: Predictive role of repair enzymes in the efficacy of Cisplatin combinations in pancreatic and lung cancer.
abstract: Platinum combinations are the mainstay of treatment for non-small cell lung cancer (NSCLC), while for pancreatic cancer platinum combinations are being given to good-performance status patients. These platinum combinations consist of cis- or carboplatin with gemcitabine, while, for non-squamous NSCLC and mesothelioma, of pemetrexed. The combination of gemcitabine and cisplatin is based on gemcitabine-induced increased formation and retention of DNA-platinum adducts, which can be explained by a decrease of excision repair cross-complementing group-1 (ERCC1)-mediated DNA repair. In these patients, survival and response is prolonged when ERCC1 has a low protein or mRNA expression. A low expression of ribonucleotide reductase (RR) is related to a better treatment outcome after both gemcitabine and gemcitabine-platinum combinations. For pemetrexed combinations, ERCC1 expression was not related to survival. For both NSCLC and pancreatic cancer, polymorphisms in ERCC1 (C118T) and Xeroderma pigmentosum group D (XPD) (A751C) were related to survival. In currently ongoing and future prospective studies, patients should be selected based on their DNA repair status, but it still has to be determined whether this should be by immunohistochemistry, mRNA expression, or a polymorphism.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands. gj.peters@vumc.nl.
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Avan
authors.forename: Marielle Gallegos
authors.initials: MG
authors.lastname: Ruiz
authors.forename: Vanessa
authors.initials: V
authors.lastname: Orsini
authors.forename: Amir
authors.initials: A
authors.lastname: Avan
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D045643:DNA Repair Enzymes / Q000378:metabolism*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011379:Prognosis; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D003841:Deoxycytidine; D016190:Carboplatin; D045643:DNA Repair Enzymes; D002945:Cisplatin; D000093542:Gemcitabine
keywords: DNA repair; ERCC1; Non-small cell lung cancer; XPD; cisplatin; gemcitabine; pancreatic cancer; review; ribonucleotide reductase