Pharmacodynamic and pharmacogenomic study of the nanoparticle conjugate of camptothecin CRLX101 for the treatment of cancer

Shikha Gaur, Yafan Wang, Leo Kretzner, Linling Chen, Terence Yen, Xiwei Wu, Yate Ching Yuan, Mark Davis, Yun Yen

研究成果: 雜誌貢獻文章同行評審

49 引文 斯高帕斯(Scopus)

摘要

CRLX101 is a nanopharmaceutical consisting of cyclodextrin-based polymer molecule and camptothecin. The CRLX101 nanoparticle is designed to concentrate and slowly release camptothecin in tumors over an extended period of time. Tumor biopsy and blood samples collected from patients with advanced solid malignancies before and after CRLX101 treatment are subjected to immunohistochemistry and pharmacogenomics. The expression of Topoisomerase-1, Ki-67, CaIX, CD31 and VEGF decreased after CRLX101 treatment. The expressions of these proteins are inversely proportional with survival duration of the patients. The Drug Metabolism Enzymes and Transporters (DMET) array shows an allele frequency in patients similar to global populations with none of the SNPs associated with toxicity. The results suggest that the observed lower toxicity is not likely to be due to different genotypes in SNPs. CRLX101 demonstrates a promising anti-tumor activity in heavily pre-treated or treatment-refractory solid tumor malignancies presumably by inhibition of proliferation and angiogenesis correlating with tumor growth inhibition. From the Clinical Editor: In this cancer treatment study clinical samples collected from patients were subjected to immunohistochemistry and pharmacogenomics. The expressions of key proteins that are inversely proportional with survival duration of the patients decreased after treatment with CRLX101, a camptothecin slow-release nanoparticle conjugate. This anti-tumor activity in heavily pre-treated and treatment resistant solid tumors, promises a novel therapeutic approach.
原文英語
頁(從 - 到)1477-1486
頁數10
期刊Nanomedicine: Nanotechnology, Biology, and Medicine
10
發行號7
DOIs
出版狀態已發佈 - 10月 1 2014
對外發佈

ASJC Scopus subject areas

  • 分子醫學
  • 生物工程
  • 生物醫學工程
  • 材料科學(全部)
  • 醫藥(雜項)
  • 藥學科學
  • 醫藥 (全部)

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