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Expression of breast cancer resistance protein is associated with a poor clinical outcome in patients with small-cell lung cancer.

AbstractBACKGROUND:
ATP-binding cassette (ABC) transporter and DNA excision repair proteins play a pivotal role in the mechanisms of drug resistance. The aim of this study was to investigate the expression of ABC transporter and DNA excision repair proteins, and to elucidate the clinical significance of their expression in biopsy specimens from patients with small-cell lung cancer (SCLC).
METHODS:
We investigated expression of the ABC transporter proteins, P-glycoprotein (Pgp), multidrug resistance associated-protein 1 (MRP1), MRP2, MRP3, and breast cancer resistance protein (BCRP), and the DNA excision repair proteins, excision repair cross-complementation group 1 (ERCC1) protein and breast cancer susceptibility gene 1 (BRCA1) protein, in tumor biopsy specimens obtained before chemotherapy from 130 SCLC patients who later received platinum-based combination chemotherapy, and investigated the relationship between their expression and both response and survival.
RESULTS:
No significant associations were found between expression of Pgp, MRP1, MRP2, MRP3, ERCC1, or BRCA1 and either response or survival. However, there was a significant association between BCRP expression and both response (p=0.026) and progression-free survival (PFS; p=0.0103).
CONCLUSIONS:
BCRP expression was significantly predictive of both response and progression-free survival (PFS) in SCLC patients receiving chemotherapy. These findings suggest that BCRP may play a crucial role in drug resistance mechanisms, and that it may serve as an ideal molecular target for the treatment of SCLC.
AuthorsYoung Hak Kim, Genichiro Ishii, Koichi Goto, Shuji Ota, Kaoru Kubota, Yukinori Murata, Michiaki Mishima, Nagahiro Saijo, Yutaka Nishiwaki, Atsushi Ochiai
JournalLung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 65 Issue 1 Pg. 105-11 (Jul 2009) ISSN: 1872-8332 [Electronic] Ireland
PMID19036469 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • DNA-Binding Proteins
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • ERCC1 protein, human
  • Endonucleases
Topics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 (biosynthesis)
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters (biosynthesis)
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, pathology)
  • DNA-Binding Proteins (biosynthesis)
  • Endonucleases (biosynthesis)
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms (drug therapy, metabolism, pathology)
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Proteins (biosynthesis)
  • Multivariate Analysis
  • Neoplasm Proteins (biosynthesis)
  • Retrospective Studies
  • Treatment Outcome

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