Under the direction of Gerald Fetterly, PhD (ET), the Pharmacokinetics/Pharmacodynamics (PK/PD) Shared Resource has grown significantly since the last CCSG grant renewal. Previously, the PK/PD Shared Resource had two divisions, which have now been consolidated to streamline processes and promote further integration and collaboration among investigators. The PK/PD Shared Resource has developed several new bioanalytical assays that support RPCI research efforts, including quantitation of drugs and biological species such as FAK inhibitors, topoisomerase inhibitors, antimetabolites, taxanes, doxorubicin, HDAC, TKl and mTOR inhibitors. These assays support ongoing investigator-initiated studies in five research programs (ET, CSBT, PS, GU, and Til). In addition, the Resource has bioanalytical assays to support chemoprevention studies, such as lignans for breast cancer prevention (PS), and nicotine and its metabolites to support smoking cessation (PS) projects. PK/PD staff utilize four state-of-the-art LC/MS/MS instruments, which detect eight androgens in plasma, bone marrow, and prostate tumor tissue at very low titers (GU). This has also improved the ability to detect topoisomerase in core biopsies (ET). Most recently, the Resource has developed a pharmacologically-driven mathematical PK/PD model to optimize anti-angiogenic treatment in AML, enhancing chemotherapy effectiveness. The Resource provides a complete service from methods development and validation to sample handling and analysis to PK/PD modeling and simulation, leading to informed decision-making about dosing, dose scheduling, and drug combinations. Data analysis using mathematical models to assess PK/PD relationships has led to presentations at national meetings, grant funding (i.e. ROl, NCCN, U01), and collaborative publications. The Shared Resource Director and/or other appropriate personnel provide initial consultation to users to discuss the scope of a project. Investigators are required to submit a sample submission form outlining what samples are being submitted to the Resource and what analyses are to be performed. Training is provided on an as-needed basis to qualified users who are interested in utilizing the Resource instrumentation. First priority for use is given to peer-review-funded RPCI CCSG members;second priority to non-peer-review- funded CCSG members;third priority to non-members and academic collaborators;and last priority to external users. During the reporting period, the PK/PD Shared Resource has served 17 members from 6 research programs, with 17% utilization by CCSG members with peer reviewed funding. The CCSG support provides 4% of the overall proposed budget.

Public Health Relevance

Understanding drug disposition is critical for relating toxicities and treatment response. Pharmacokinetic studies are crucial in early drug development for understanding how the body reacts to a drug or agent, which is critical in dosing and therapy optimization. The PK/PD resource is essential for novel early phase clinical research, drug/agent development, and translational research.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA016056-37
Application #
8933331
Study Section
Subcommittee G - Education (NCI)
Program Officer
Ciolino, Henry P
Project Start
2014-06-26
Project End
2019-04-30
Budget Start
2014-06-26
Budget End
2015-04-30
Support Year
37
Fiscal Year
2014
Total Cost
$64,027
Indirect Cost
$25,325
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
824771034
City
Buffalo
State
NY
Country
United States
Zip Code
14263
Clyde, Merlise A; Palmieri Weber, Rachel; Iversen, Edwin S et al. (2016) Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci. Am J Epidemiol 184:579-589
Wilton, John; Kurenova, Elena; Pitzonka, Laura et al. (2016) Pharmacokinetic analysis of the FAK scaffold inhibitor C4 in dogs. Eur J Drug Metab Pharmacokinet 41:55-67
Zhao, Zhiguo; Wen, Wanqing; Michailidou, Kyriaki et al. (2016) Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry. Cancer Causes Control 27:679-93
Goossens, Maria E; Isa, Fatima; Brinkman, Maree et al. (2016) International pooled study on diet and bladder cancer: the bladder cancer, epidemiology and nutritional determinants (BLEND) study: design and baseline characteristics. Arch Public Health 74:30
Pharoah, Paul D P; Song, Honglin; Dicks, Ed et al. (2016) PPM1D Mosaic Truncating Variants in Ovarian Cancer Cases May Be Treatment-Related Somatic Mutations. J Natl Cancer Inst 108:
Austin, David C; Strand, Douglas W; Love, Harold L et al. (2016) NF-κB and androgen receptor variant 7 induce expression of SRD5A isoforms and confer 5ARI resistance. Prostate 76:1004-18
Sexton, Sandra; Tulowitzki, Ryan; Jones, Craig A et al. (2016) Involvement of the renin-angiotensin system in the development of nephrogenic systemic fibrosis-like lesions in the RenTag mouse model. Clin Exp Nephrol 20:162-8
Shafirstein, Gal; Battoo, Athar; Harris, Kassem et al. (2016) Photodynamic Therapy of Non-Small Cell Lung Cancer. Narrative Review and Future Directions. Ann Am Thorac Soc 13:265-75
Bistulfi, Gaia; Affronti, Hayley C; Foster, Barbara A et al. (2016) The essential role of methylthioadenosine phosphorylase in prostate cancer. Oncotarget 7:14380-93
Rohrbach, Daniel J; Rigual, Nestor; Arshad, Hassan et al. (2016) Intraoperative optical assessment of photodynamic therapy response of superficial oral squamous cell carcinoma. J Biomed Opt 21:18002

Showing the most recent 10 out of 1099 publications