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
Miller, James A; Harris, Kassem; Roche, Charles et al. (2018) Sarcopenia is a predictor of outcomes after lobectomy. J Thorac Dis 10:432-440
Fenstermaker, Robert A; Figel, Sheila A; Qiu, Jingxin et al. (2018) Survivin Monoclonal Antibodies Detect Survivin Cell Surface Expression and Inhibit Tumor Growth In Vivo. Clin Cancer Res 24:2642-2652
Bhat, Tariq A; Kalathil, Suresh Gopi; Bogner, Paul N et al. (2018) Secondhand Smoke Induces Inflammation and Impairs Immunity to Respiratory Infections. J Immunol 200:2927-2940
Merzianu, Mihai; Groman, Adrienne; Hutson, Alan et al. (2018) Trends in Bone Marrow Sampling and Core Biopsy Specimen Adequacy in the United States and Canada: A Multicenter Study. Am J Clin Pathol 150:393-405
Qin, Bo; Llanos, Adana A M; Lin, Yong et al. (2018) Validity of self-reported weight, height, and body mass index among African American breast cancer survivors. J Cancer Surviv 12:460-468
Qiao, Guanxi; Chen, Minhui; Bucsek, Mark J et al. (2018) Adrenergic Signaling: A Targetable Checkpoint Limiting Development of the Antitumor Immune Response. Front Immunol 9:164
Kumar, Sandeep; Inigo, Joseph R; Kumar, Rahul et al. (2018) Nimbolide reduces CD44 positive cell population and induces mitochondrial apoptosis in pancreatic cancer cells. Cancer Lett 413:82-93
Liu, Chunhong; Yu, Tao; Xing, Zhuo et al. (2018) Triplications of human chromosome 21 orthologous regions in mice result in expansion of megakaryocyte-erythroid progenitors and reduction of granulocyte-macrophage progenitors. Oncotarget 9:4773-4786
Muramatsu, Masashi; Akakura, Shin; Gao, Lingqiu et al. (2018) SSeCKS/Akap12 suppresses metastatic melanoma lung colonization by attenuating Src-mediated pre-metastatic niche crosstalk. Oncotarget 9:33515-33527
Gurova, Katerina; Chang, Han-Wen; Valieva, Maria E et al. (2018) Structure and function of the histone chaperone FACT - Resolving FACTual issues. Biochim Biophys Acta Gene Regul Mech :

Showing the most recent 10 out of 1555 publications