<i>ERCC1</i> and Thymidylate Synthase mRNA Levels Predict Survival for Colorectal Cancer Patients Receiving Combination Oxaliplatin and Fluorouracil Chemotherapy

Shirota, Yoshinori; Stoehlmacher, Jan; Brabender, Jan; Xiong, Yi-Ping; Uetake, Hiroyuki; Danenberg, Kathleen D.; Groshen, Susan; Tsao-Wei, Denise D.; Danenberg, Peter V.; Lenz, Heinz‐Josef

doi:10.1200/jco.2001.19.23.4298

Cited by 586 publications

(436 citation statements)

References 26 publications

Supporting

Mentioning

402

Contrasting

Unclassified

Order By: Relevance

“…Previous studies have tested ERCC1 mRNA expression in paraffin-embedded tumour samples in advanced colorectal cancer patients treated with 5-FU plus oxaliplatin (Shirota et al, 2001) and in non-small-cell lung cancer patients treated with gemcitabine plus cisplatin (Lord et al, 2002); both studies found a significant association between ERCC1 expression and survival. Cisplatin resistance is multifactorial, also involving the copper transporter ATP7A (Chen et al, 2007) and a 45-gene expression signature was a predictor of cisplatin sensitivity with 83% accuracy (Hsu et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOLFOX regimen

et al. 2008

View full text Add to dashboard Cite

Molecular markers involved in DNA repair can help to predict survival in gastric cancer patients treated with 5-FU plus platinum chemotherapy. Excision repair cross-complementing 1 (ERCC1) and thymidylate synthase (TS) mRNA expression levels were assessed in advanced gastric cancer tumour samples using real-time quantitative PCR in 76 patients treated with a modified FOLFOX (biweekly oxaliplatin plus 5-FU and folinic acid) regimen. Median survival time in patients with low ERCC1 levels was significantly longer than in those with high levels (15.8 vs 6.2 months; Po0.0001). Patients with high TS levels had longer survival than those with low levels (12.2 vs 10.1 months; P ¼ 0.01). Forty-eight patients with low ERCC1 and high TS levels had a median survival of 16.1 months (Po0.0001). The hazard ratio for patients with high ERCC1 expression was 9.4 (Po0.0001). In patients with high mRNA levels of ERCC1, alternative chemotherapy regimens should be considered.

show abstract

Section: Discussionmentioning

confidence: 99%

ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOLFOX regimen

et al. 2008

View full text Add to dashboard Cite

show abstract

“…64 More recently, the same group has reported that survival of patients with metastatic CRC following 5FU/oxaliplatin chemotherapy was significantly better in patients expressing low levels of ERCC1 mRNA compared to those expressing high levels. 65 It appears from this study that ERCC1 is an independent predictive marker of response to 5FU/oxaliplatin chemotherapy. Other proteins involved in nucleotide excision repair such as ERCC2 and XPF may also affect the ability of tumour cells to remove DNAplatinum adducts and should be assessed in future studies.…”

Section: Platinum Compoundsmentioning

confidence: 66%

Clinical significance of prognostic and predictive markers in colorectal cancer

2002

View full text Add to dashboard Cite

“…Although it is possible to establish a pattern of acquired genetic expression resistance to oxaliplatin in vitro [2], most studies in the literature analyse specifi c genes. As the authors mention, the response to oxaliplatin has been signifi cantly related to ERCC1 expression [3,4], and also to the association of ERCC1 and TS levels [5], although with a predictive value a bit lower than 65-68%. The presence of polymorphisms in these genes modulates their expression and the possibility of being determined in peripheral blood makes its analysis easier.…”

Section: Oxaliplatin Colorectal Cancer and Predictive Factors Albertmentioning

confidence: 99%

Oxaliplatin, colorectal cancer and predictive factors

Esteve

2011

Clin Transl Oncol

View full text Add to dashboard Cite

T he search for predictive factors of response is one of today's greatest challenges in modern oncology. At a time at which the complexity and the cost of treatment are becoming higher and higher, we think it is of great importance to be able to have predictive factors that allow us to avoid unnecessary treatments as well as optimising them for those patients who are sensitive. The approaches to this problem are diverse and involve different groups of drugs and different analysis techniques depending on the specifi c drug and the goal of the analysis. We have the clearest example in the predictive value of the presence of kras mutations in the response to the treatment with anti-EGFR drugs, which together with HERB2 expression in the treatment with trastuzumab constitute the only accepted predictive factors in digestive cancer. Probably, the so-called biologic drugs or therapeutic targets, acting on a very particular aspect of the modes of signal transmission, are sensitive to very specifi c and concrete markers. The same is not true, however, for the chemotherapy drugs that could be considered "classical", which, on the other hand, continue to be the essential support for colorectal cancer treatment as well as for most tumours. In this fi eld, the analysis of polymorphisms is the most developed in advanced cancer although some other genetic signatures with prognostic value and with possible usefulness in the decision making of adjuvant treatment have been developed. In this volume of Clinical and Translational Oncology, Watanabe et al. introduce us in their article to microarray analysis as a method to obtain a pattern of resistance or sensitivity to oxaliplatin in 40 metastatic patients treated with FOLFOX6 [1]. From the analysis we obtain a genetic signature of 27 genes whose expression determines the response to treatment with 89.7% of positive predictive value and 100% negative, which equals the kras mutation for antiEGFR agents. One of the diffi culties in fi nding sensitive markers is the fact that patients are treated with drug associations that alter the effect that a marker can have on a specifi c drug. The genetic signature applied to a polychemotherapy scheme can be an advantage in this sense since it analyses it as a whole and not as a concrete point of the cellular metabolism valid for the target agents but probably too concrete for chemotherapy. Although it is possible to establish a pattern of acquired genetic expression resistance to oxaliplatin in vitro [2], most studies in the literature analyse specifi c genes. As the authors mention, the response to oxaliplatin has been signifi cantly related to ERCC1 expression [3,4], and also to the association of ERCC1 and TS levels [5], although with a predictive value a bit lower than 65-68%. The presence of polymorphisms in these genes modulates their expression and the possibility of being determined in peripheral blood makes its analysis easier. The analysis of polymorphisms in repair genes, especially ERCC1 and XRCC1 associated or not with TS polymo...

show abstract

ERCC1 and Thymidylate Synthase mRNA Levels Predict Survival for Colorectal Cancer Patients Receiving Combination Oxaliplatin and Fluorouracil Chemotherapy

Cited by 586 publications

References 26 publications

ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOLFOX regimen

ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOLFOX regimen

Clinical significance of prognostic and predictive markers in colorectal cancer

Oxaliplatin, colorectal cancer and predictive factors

Contact Info

Product

Resources

About