title: Application of sequential factorial design and orthogonal array composite design (OACD) to study combination of 5 prostate cancer drugs.
abstract: Prostate cancer is one of the most common cancers among men in the United States. It is also a major leading cause of cancer death among men of all races. In order to treat prostate cancer, drug combinations are often applied. Drug combinations target at different pathways of cells can potentially lead to higher efficacy and lower toxicity due to drug synergy. In this paper, we sequentially applied a two-level design and a follow-up orthogonal array composite design (OACD) to investigate combinations of five anti-cancer drugs, namely, doxorubicin, docetaxel, paclitaxel, cis-dichlorodiamine platinum and dihydroartemisinin. Our initial screening using a two-level full factorial design identified doxorubicin and docetaxel as the most significant drugs. A follow-up experiment with an OACD revealed more complicated drug interactions among these 5 anti-cancer drugs. Quadratic effects of doxorubicin and paclitaxel appeared to be significant. A further investigation on contour plots of all the two-drug pairs indicated that combination of doxorubicin and docetaxel are the most effective companion, while the combination of cis-dichlorodiamine platinum and dihydroartemisinin showed unknown antagonistic effects which diminished the individual drug anti-cancer efficacy. These observations have significant practical implications in the understanding of anti-cancer drug mechanism that can facilitate clinical practice of better drug combinations.
authors.affiliation: Department of Urology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China; School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Jia
authors.affiliation: School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Alok
authors.initials: A
authors.lastname: Sharma
authors.affiliation: School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Urology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China.
authors.forename: Guohai
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Urology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China.
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Urology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Urology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China. Electronic address: dongbaba2@hotmail.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address: dingxianting@sjtu.edu.cn.
authors.forename: Xianting
authors.initials: X
authors.lastname: Ding
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D008297:Male; D015233:Models, Statistical; D017239:Paclitaxel / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012044:Regression Analysis; D043823:Taxoids / Q000494:pharmacology
chemical_list: D037621:Artemisinins; D043823:Taxoids; D000077143:Docetaxel; C039060:artenimol; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin
keywords: Anticancer; Drug combination; Factorial design; Orthogonal array composite design; Stepwise regression