Pharmacogenomics of gemcitabine in non-small-cell lung cancer and other solid tumors

被引：44

作者：

Danesi, Romano ^{[1
]}

Altavilla, Giuseppe ^{[2
]}

Giovannetti, Elisa ^{[1
]}

Rosell, Raffael ^{[3
]}

机构：

[1] Univ Pisa, Div Pharmacol & Chemotherapy, Dept Internal Med, I-56126 Pisa, Italy

[2] Univ Messina, Dept Med Oncol, I-98100 Messina, Italy

[3] Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, Barcelona, Spain

来源：

PHARMACOGENOMICS | 2009年 / 10卷 / 01期

关键词：

gemcitabine; metabolism; non-small-cell lung cancer; NSCLC; pancreatic cancer; pharmacogenetics; targets; uptake; SINGLE-NUCLEOTIDE POLYMORPHISMS; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER-1; MESSENGER-RNA EXPRESSION; CYTIDINE-DEAMINASE GENE; DEOXYCYTIDINE KINASE; RIBONUCLEOTIDE REDUCTASE; PANCREATIC-CANCER; IN-VITRO; FUNCTIONAL-CHARACTERIZATION; DNA-REPAIR;

D O I：

10.2217/14622416.10.1.69

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The validation of predictive biomarkers to tailor chemotherapy is a key issue in the development of effective treatment modalities against cancer. Examples of how genetics might affect drug response are offered by gemcitabine. A substantial number of potential biomarkers for sensitivity or resistance to gemcitabine have been proposed, including ribonucleotide reductase and cytidine deaminase polymorphisms, human equilibrative transporter-1 and ribonucleotide reductase gene-expression and AKT phosphorylation status. These markers displayed a significant relationship with disease response to the drug; however, their robustness needs to be evaluated within prospective studies. Moreover, recent trials of customized chemotherapy based on genetic markers have been carried out in non-small-cell lung cancer and promising pharmacogenetic determinants are gaining momentum, including BRCA1 and ERCC1. Hopefully, biomarkers to select patients most likely to respond to gemcitabine will be validated in the near future.

引用

页码：69 / 80

页数：12

共 107 条

[1] Determinants of sensitivity and resistance to gemcitabine: The roles of human equilibrative nucleoside transporter 1 and deoxycytidine kinase in non-small cell lung cancer [J].

Achiwa, H ;

Oguri, T ;

Sato, S ;

Maeda, H ;

Niimi, T ;

Ueda, R .

CANCER SCIENCE, 2004, 95 (09) :753-757

[2] Detection of an alternatively spliced form of deoxycytidine kinase mRNA in the 2′-2′-difluorodeoxycytidine (gemcitabine)-resistant human ovarian cancer cell line AG6000 [J].

Al-Madhoun, AS ;

van der Wilt, CL ;

Loves, WJP ;

Padron, JM ;

Eriksson, S ;

Talianidis, I ;

Peters, GJ .

BIOCHEMICAL PHARMACOLOGY, 2004, 68 (04) :601-609

[3] The ERCC1/XPF endonuclease is required for efficient single-strand annealing and gene conversion in mammalian cells [J].

Al-Minawi, Ali Z. ;

Saleh-Gohari, Nasrollah ;

Helleday, Thomas .

NUCLEIC ACIDS RESEARCH, 2008, 36 (01) :1-9

[4] Excellent response to gemcitabine in a massively pre-treated woman with extensive cutaneous involvement after recurrence of breast cancer [J].

Arends, J ;

Unger, C .

INVESTIGATIONAL NEW DRUGS, 2001, 19 (01) :93-100

[5] Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma [J].

Bengala, C ;

Guarneri, V ;

Giovannetti, E ;

Lencioni, M ;

Fontana, E ;

Mey, V ;

Fontana, A ;

Boggi, U ;

Del Chiaro, M ;

Danesi, R ;

Ricci, S ;

Mosca, F ;

Del Tacca, M ;

Conte, PF .

BRITISH JOURNAL OF CANCER, 2005, 93 (01) :35-40

[6] Ribonucleotide reductase M1 gene promoter activity, polymorphisms, population frequencies, and clinical relevance [J].

Bepler, G ;

Zheng, Z ;

Gautam, A ;

Sharma, S ;

Cantor, A ;

Sharma, A ;

Cress, WD ;

Kim, YC ;

Rosell, R ;

McBride, C ;

Robinson, L ;

Sommers, E ;

Haura, E .

LUNG CANCER, 2005, 47 (02) :183-192

[7] RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer [J].

Bepler, Gerold ;

Kusmartseva, Irina ;

Sharma, Swati ;

Gautam, Ashish ;

Cantor, Alan ;

Sharma, Anupama ;

Simon, George .

JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (29) :4731-4737

[8] Decreased resistance to gemcitabine (2′,2′-difluorodeoxycitidine) of cytosine arabinoside-resistant myeloblastic murine and rat leukemia cell lines:: Role of altered activity and substrate specificity of deoxycytidine kinase [J].

Bergman, AM ;

Pinedo, HM ;

Jongsma, APM ;

Brouwer, M ;

van Haperen, VWTR ;

Veerman, G ;

Leyva, A ;

Eriksson, S ;

Peters, GJ .

BIOCHEMICAL PHARMACOLOGY, 1999, 57 (04) :397-406

[9] Increased sensitivity to gemcitabine of P-glycoprotein and multidrug resistance-associated protein-overexpressing human cancer cell lines [J].

Bergman, AM ;

Pinedo, HM ;

Talianidis, I ;

Veerman, G ;

Loves, WJP ;

van der Wilt, CL ;

Peters, GJ .

BRITISH JOURNAL OF CANCER, 2003, 88 (12) :1963-1970

[10] In vivo induction of resistance to gemcitabine results in increased expression of ribonucleotide reductase subunit M1 as the major determinant [J].

Bergman, AM ;

Eijk, PP ;

van Haperen, VWTR ;

Smid, K ;

Veerman, G ;

Hubeek, I ;

van den Ijssel, P ;

Ylstra, B ;

Peters, GJ .

CANCER RESEARCH, 2005, 65 (20) :9510-9516

← 1 2 3 4 5 6 7 8 9 10 →