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

Gaur, Shikha and Wang, Yafan and Kretzner, Leo and Chen, Linling and Yen, Terence and Wu, Xiwei and Yuan, Yate-Ching and Davis, Mark and Yen, Yun (2014) Pharmacodynamic and Pharmacogenomic study of the nanoparticle conjugate of camptothecin CRLX101 for the treatment of cancer. Nanomedicine-Nanotechnology Biology and Medicine, 10 (7). pp. 1477-1486. ISSN 1549-9634. doi:10.1016/j.nano.2014.04.003. https://resolver.caltech.edu/CaltechAUTHORS:20140505-152718789

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Abstract

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 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.nano.2014.04.003DOIArticle
http://www.sciencedirect.com/science/article/pii/S1549963414001865PublisherArticle
http://www.nanomedjournal.com/article/S1549-9634%2814%2900186-5/abstractPublisherArticle
ORCID:
AuthorORCID
Davis, Mark0000-0001-8294-1477
Yen, Yun0000-0003-0815-412X
Additional Information:© 2014 Elsevier B.V. Received date: 3 January 2014. Revised date: 7 April 2014. Accepted date: 10 April 2014. We thank Ms. Sofia Loera for histopathological staining, Ms. Mariko Lee with microscope imaging, Dr. Lufen Chang for helpful suggestions, Dr. Xiyong Liu for statistical analysis, and Scott Eliasof, Edward Garmey and Andre Zahn for editing of the manuscript.
Subject Keywords:Camptothecin; Nanoparticle; Polymer conjugate; Topoisomerase 1; HIF-1α; Immunohistochemistry; Solid tumor
Issue or Number:7
DOI:10.1016/j.nano.2014.04.003
Record Number:CaltechAUTHORS:20140505-152718789
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20140505-152718789
Official Citation:Pharmacodynamic and pharmacogenomic study of the nanoparticle conjugate of camptothecin CRLX101 for the treatment of cancer Potential Clinical Relevance Shikha Gaur, Yafan Wang, Leo Kretzner, Linling Chen, Terence Yen, Xiwei Wu, Yate-Ching Yuan, Mark Davis, Yun Yen p1477–1486 Published online: April 24, 2014
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:45506
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:06 May 2014 16:37
Last Modified:10 Nov 2021 17:04

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