Gene Expression as a Predictive Marker of Outcome in Stage IIB-IIIA-IIIB Non-Small Cell Lung Cancer After Induction Gemcitabine-Based Chemotherapy Followed By Resectional Surgery

Rosell, Rafael; Felip, Enriqueta; Tarón, Miquel; Majó, Joaquim; Méndez, Pedro Rafael Casado; Sanchez-Ronco, María; Queralt, Cristina; Sánchez, José Javier; Maestre, José

doi:10.1158/1078-0432.ccr-040006

Cited by 123 publications

(88 citation statements)

References 20 publications

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“…Furthermore, two clinical studies have demonstrated that the assessment of hENT1 and RRM1 is useful in order to predict the response to gemcitabine in pancreas and lung cancer, respectively (38,53). Our previous study has also indicated the importance of RRM1 as a possible chemoresistance marker for gemcitabine in BTC (48).…”

Section: Discussionmentioning

confidence: 98%

Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma

Nakamura

Kohya²,

Kai³

et al. 2010

Int J Oncol

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Abstract. Gemcitabine is a commonly used chemotherapeutic agent for advanced biliary tract carcinoma (BTC), although its efficacy is insufficient. Therefore, it is essential to establish new diagnostic methods, which can predict responders before the treatment. The aim of this study is to identify the most reliable chemoresistance marker to gemcitabine in BTC among the 4 molecules (hENT1, dCK, RRM1 and RRM2) involved in gemcitabine metabolism. The expression of 4 molecules were investigated in 5 BTC cell lines, and correlated with gemcitabine sensitivity. RRM1 protein was also assessed by quantitative double-fluorescence immunohistochemistry (qDFIHC) in 10 patients with unresectable or recurrent BTC who received gemcitabine-based chemotherapy. RRM1 and RRM2 protein strongly correlated with the IC 50 value for gemcitabine in BTC cell lines (R=0.935, 0.771, respectively). In addition, patients with low RRM1 were significantly more sensitive to gemcitabine (p=0.033), and their survival was significantly better than patients with high RRM1 (p=0.001).In conclusion, RRM1 particularly in protein level is a reliable marker for gemcitabine resistance in BTC. Furthermore, qDFIHC is a useful method for the assessment of RRM1 protein, in order to design a tailor-made chemotherapeutic regimen for BTC patients.

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Section: Discussionmentioning

confidence: 98%

Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma

Nakamura

Kohya²,

Kai³

et al. 2010

Int J Oncol

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“…RRM1 has been shown to function with the p53-regulated RRM2 homologue p53R2, which is important in DNA repair secondary to genotoxic stress [11]. In in vitro studies, increased RRM1 expression and activity has been shown to be a marker for gemcitabine resistance [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

An Association Between RRM1 Haplotype and Gemcitabine-Induced Neutropenia in Breast Cancer Patients

Rha

Jeung²,

Choi

et al. 2007

The Oncologist

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Purpose. We examined the pattern of single-nucleotide polymorphisms (SNPs) of gemcitabine metabolism-related and target genes in breast cancer patients and evaluated their association with drug response or toxicity.Patients and Methods. SNPs in deoxycytidine kinase (dCK), deoxycytidine monophosphate deaminase (DCTD), and ribonucleotide reductase M1 polypeptide (RRM1) were analyzed with genomic DNA of 10 breast cancer cell lines, 74 peripheral blood mononuclear cell (PBMC) samples from advanced breast cancer patients treated with gemcitabine, and 56 PBMC samples from healthy volunteers.Results. Disclosure of potential conflicts of interest is found at the end of this article.

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“…This highlights the multifactorial nature of platinum resistance and therefore the difficulty in using DNA repair proteins as markers of platinum resistance in the clinic. Some trials have found an association between ERCC1 and response to cisplatin combination therapy [28][29][30], but many more have found no association [31][32][33][34][35]. High ERCC1 may correlate with platinum resistance, but low or absent ERCC1 may not always indicate sensitivity as the H69CIS200 and H69OX400 when actively dividing show no change in ERCC1 despite being platinum resistant.…”

Section: No Change In Dna Repair Capacity Associated With Platinum Rementioning

confidence: 99%

ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair

Stordal

Davey

2008

Cancer Chemother Pharmacol

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Gene Expression as a Predictive Marker of Outcome in Stage IIB-IIIA-IIIB Non-Small Cell Lung Cancer After Induction Gemcitabine-Based Chemotherapy Followed By Resectional Surgery

Abstract: Patients with RRM1 levels in the bottom quartile benefited significantly from gemcitabine/cisplatin neoadjuvant chemotherapy, leading us to conclude that RRM1 mRNA levels should be additionally validated to proceed with tailored chemotherapy.

Cited by 123 publications

References 20 publications

Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma

Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma

An Association Between RRM1 Haplotype and Gemcitabine-Induced Neutropenia in Breast Cancer Patients

ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair

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