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17.09.2019 | Original Article

ABCC11 gene polymorphism as a potential predictive biomarker for an oral 5-fluorouracil derivative drug S-1 treatment in non-small cell lung cancer

verfasst von: Takehiro Uemura, Tetsuya Oguri, Ken Maeno, Kazuki Sone, Akira Takeuchi, Satoshi Fukuda, Eiji Kunii, Osamu Takakuwa, Yoshihiro Kanemitsu, Hirotsugu Ohkubo, Masaya Takemura, Yutaka Ito, Akio Niimi

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 6/2019

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Abstract

Purpose

ABCC11/MRP8 (ABCC11) is an ATP-binding cassette transporter that is involved in regulating cellular sensitivity and resistance for many anti-cancer drugs. Since 5-fluorouracil (5-FU) is one of the substrates for ABCC11, we examined whether ABCC11 is a predictive marker for an oral 5-FU derivative drug S-1 treatment in non-small cell lung cancer (NSCLC).

Methods

Real-time PCR and MTS assay were carried on 21 human NSCLC cell lines. The drug resistance capabilities of ABCC11 are evaluated by analyzing the resistance profiles of a clone of HeLa cell in which the pump was ectopically expressed. Blood samples of 106 NSCLC patients were collected.

Results

There was a significant correlation between dihydropyrimidine dehydrogenase (DPD) gene expression and the IC₅₀ for 5-FU. We then classified NSCLC cell lines into two groups based on the phenotype of the SNP538 (G > A) in ABCC11: a combined G/G and G/A group, and an A/A group. The distribution of the IC₅₀ for 5-FU in combination with a potent inhibitor of DPD 5-chloro-2, 4-dihydropyrimidine (CDHP), which is contained in S-1, showed a significant reduction in the A/A group compared with the combined G/G and G/A group. Next, the clinical usefulness of the ABCC11 SNP in treatment containing S-1 was examined in 106 NSCLC patients, and the disease control rate was found to be significantly better in the A/A group than in the combined G/G and G/A group.

Conclusions

These results indicate that the SNP538(G > A) in the ABCC11 gene is a potential determinant for S-1 treatment.

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Titel: ABCC11 gene polymorphism as a potential predictive biomarker for an oral 5-fluorouracil derivative drug S-1 treatment in non-small cell lung cancer
verfasst von: Takehiro Uemura
Tetsuya Oguri
Ken Maeno
Kazuki Sone
Akira Takeuchi
Satoshi Fukuda
Eiji Kunii
Osamu Takakuwa
Yoshihiro Kanemitsu
Hirotsugu Ohkubo
Masaya Takemura
Yutaka Ito
Akio Niimi
Publikationsdatum: 17.09.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 6/2019
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-03959-3

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ABCC11 gene polymorphism as a potential predictive biomarker for an oral 5-fluorouracil derivative drug S-1 treatment in non-small cell lung cancer

Abstract

Purpose

Methods

Results

Conclusions

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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