This is a revised clinical- and translational-based interdisciplinary Program Project Grant application entitled """"""""Chinese Herbal Medicine as a Novel Paradigm for Cancer Chemotherapy"""""""". The Pl of this Program is Yung-chi Cheng, Ph.D., and he directs Project 2. He is joined two other well-established Project leaders, Edward Chu, M.D. (Project 1), who also serves as Co-P.l. of the Program, and Hongyu Zhao, Ph.D. (Project 3). These 3 Projects are supported by an Administrative Core (Core A) and an Analytical Core (Core B). In this application, we propose to investigate PHY906, a Chinese herbal medicine that has been used in the Orient for nearly 2000 years. Our group has developed a rigorous standard operating procedure to produce cGMP material as well as develop highly sensitive chemical (LC-MS) and biological (gene expression) fingerprinting methodologies to ensure quality control and consistency of batch preparation. Using high quality cGMP material, we plan to conduct a randomized, double-blind, placebo-controlled study where PHY906 will be tested in combination with the topoisomerase I inhibitor irinotecan (CPT-11) in patients with mCRC in the 2nd- line setting. In Project 1, Dr. Chu will investigate the effect of PHY906 on the safety, health-related quality of life, and clinical efficacy of CPT-11 monotherapy. In Project 2, Dr. Cheng will conduct an extensive series of biomarker analyses to identify the potential pharmacodynamic markers that can be used to predict for the clinical activity and efficacy of PHY906 when used in combination with CPT-11. In Project 3, Dr. Zhao will develop novel bioinformatic and computational methodologies to mine the translational data coming from Project 2 with the goal of identifying the predictive biomarkers that are associated with either the cytoprotective effects of PHY906 on CPT-11 toxicity and/or the modulatory effects of PHY906 on clinical efficacy of CPT-11 chemotherapy, as determined by the studies proposed in Project 1. Several mechanisms are in place to ensure the close interaction and cohesion of the Program, and these include monthly meetings of the Project leaders, an annual retreat, and an internal advisory board to provide guidance and advice.

Public Health Relevance

This is a multi-investigator, clinical- and translational-based grant that seeks to investigate the role of a novel Chinese herbal medicine as a modulator of cancer chemotherapy in the treatment of metastatic colorectal cancer. This study may serve as a new treatment paradigm for developing herbal and/or botanical medicines in combination with cancer chemotherapy for the treatment of other human cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA154295-02
Application #
8333321
Study Section
Special Emphasis Panel (ZCA1-GRB-S (M1))
Program Officer
Xi, Dan
Project Start
2011-09-15
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$1,292,429
Indirect Cost
$406,434
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Guan, Fulan; Lam, Wing; Hu, Rong et al. (2018) Majority of Chinese Medicine Herb Category ""Qing Re Yao"" Have Multiple Mechanisms of Anti-inflammatory Activity. Sci Rep 8:7416
Tan, Hor-Yue; Wang, Ning; Lam, Wing et al. (2018) Targeting tumour microenvironment by tyrosine kinase inhibitor. Mol Cancer 17:43
Sun, Jiehuan; Herazo-Maya, Jose D; Huang, Xiu et al. (2018) Distance-correlation based gene set analysis in longitudinal studies. Stat Appl Genet Mol Biol 17:
Lam, Wing; Ren, Yongshen; Guan, Fulan et al. (2018) Mechanism Based Quality Control (MBQC) of Herbal Products: A Case Study YIV-906 (PHY906). Front Pharmacol 9:1324
Chao, Jung; Dai, Yuntao; Cheng, Hao-Yuan et al. (2017) Improving the Concentrations of the Active Components in the Herbal Tea Ingredient, Uraria crinita: The Effect of Post-harvest Oven-drying Processing. Sci Rep 7:38763
Liu, Yiyi; Zhao, Hongyu (2017) Variable importance-weighted Random Forests. Quant Biol 5:338-351
Sun, Jiehuan; Herazo-Maya, Jose D; Kaminski, Naftali et al. (2017) A Dirichlet process mixture model for clustering longitudinal gene expression data. Stat Med 36:3495-3506
Lin, Zhixiang; Wang, Tao; Yang, Can et al. (2017) On joint estimation of Gaussian graphical models for spatial and temporal data. Biometrics 73:769-779
Sun, Jiehuan; Warren, Joshua L; Zhao, Hongyu (2017) A Bayesian semiparametric factor analysis model for subtype identification. Stat Appl Genet Mol Biol 16:145-158
Zhu, Ruoqing; Zhao, Ying-Qi; Chen, Guanhua et al. (2017) Greedy outcome weighted tree learning of optimal personalized treatment rules. Biometrics 73:391-400

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