Gossypol Combined With Docetaxel and Cisplatin Scheme in Advanced Non Small-cell Lung Cancers With APE1 High Expression

Summary

The investigators' experimental study found that gossypol was the natural inhibitor of apyrimidinic endonuclease 1 (APE1) and clinical study observed that high expression of APE1 was relative to the platinum-resistance in non-small cell lung cancer. Thus the purpose of this study is to find out whether gossypol can improve the sensitivity of cisplatin-based chemotherapy in the non-small cell lung cancer with apurinic apyrimidinic endonuclease 1 (APE1) high expression

Timeline

Start

2013-09

Primary completion

2016-02

Completion

2016-09

Publications

• Background Olaussen KA, Dunant A, Fouret P, Brambilla E, Andre F, Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH, Stahel R, Sabatier L, Pignon JP, Tursz T, Le Chevalier T, Soria JC; IALT Bio Investigators. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006 Sep 7;355(10):983-91. doi: 10.1056/NEJMoa060570.
• Background Kelley MR, Georgiadis MM, Fishel ML. APE1/Ref-1 role in redox signaling: translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1. Curr Mol Pharmacol. 2012 Jan;5(1):36-53. doi: 10.2174/1874467211205010036.
• Background Wang D, Xiang DB, Yang XQ, Chen LS, Li MX, Zhong ZY, Zhang YS. APE1 overexpression is associated with cisplatin resistance in non-small cell lung cancer and targeted inhibition of APE1 enhances the activity of cisplatin in A549 cells. Lung Cancer. 2009 Dec;66(3):298-304. doi: 10.1016/j.lungcan.2009.02.019. Epub 2009 Mar 25.
• Background Sonpavde G, Matveev V, Burke JM, Caton JR, Fleming MT, Hutson TE, Galsky MD, Berry WR, Karlov P, Holmlund JT, Wood BA, Brookes M, Leopold L. Randomized phase II trial of docetaxel plus prednisone in combination with placebo or AT-101, an oral small molecule Bcl-2 family antagonist, as first-line therapy for metastatic castration-resistant prostate cancer. Ann Oncol. 2012 Jul;23(7):1803-8. doi: 10.1093/annonc/mdr555. Epub 2011 Nov 23.
• Background Ready N, Karaseva NA, Orlov SV, Luft AV, Popovych O, Holmlund JT, Wood BA, Leopold L. Double-blind, placebo-controlled, randomized phase 2 study of the proapoptotic agent AT-101 plus docetaxel, in second-line non-small cell lung cancer. J Thorac Oncol. 2011 Apr;6(4):781-5. doi: 10.1097/JTO.0b013e31820a0ea6.
• Background Bepler G, Williams C, Schell MJ, Chen W, Zheng Z, Simon G, Gadgeel S, Zhao X, Schreiber F, Brahmer J, Chiappori A, Tanvetyanon T, Pinder-Schenck M, Gray J, Haura E, Antonia S, Fischer JR. Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2013 Jul 1;31(19):2404-12. doi: 10.1200/JCO.2012.46.9783. Epub 2013 May 20.

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