This proposal provides a comprehensive plan for the career development of the applicant in cancer biomarker discovery and validation. Through mentored research, coursework and independent study, Dr. Van Poznak will develop collaborative relationships and methodologic skills to support her research agenda in pharmogenomics and toxicities of therapy. The didactic training in clinical trial design and ethics, pharmacogenomics and genetic analysis proposed will greatly expand the candidate's current training and research program. This proposal focuses on the use of novel technologies to improve assessment of risk of toxicities during cancer care, specifically by combining clinical and genetic data to establish an individualized patient specific profile of risk for developing osteonecrosis of the jaw (ONJ), an oral lesion with exposed, necrotic bone. These lesions are often associated with pain, swelling, and infection. ONJ may occur in 1- 10% of patients with cancer and bone metastases treated with intravenous nitrogen containing bisphosphonate therapy. The bisphosphonates decrease the risk of skeletal related events, such as fracture, by approximately one third and are routinely used in patients with cancer involving the bone. The overarching goal of this research proposal is to develop an index for estimating an individual's risk of developing ONJ. This index of risk will be created with the data generated from a multi-Institutional, Case Control study investigating single nucleotide polymorphisms (SNPs) within the target enzyme of the bisphosphonates, as well as investigate clinical and epidemiologic features associated with ONJ in patients with metastatic bone disease who have received intravenous bisphosphonate therapy. The identification of clinical and genetic markers correlated with risk of toxicity will lend insight into the etiology of ONJ and will provide patients and their health care providers a tool to assess risks of therapy on an individualized basis. The didactic training and mentored research activities will provide Dr Van Poznak the foundation for which she can generate highly competitive grant applications in the final years of the award and advance patient care through personalized medicine as it relates to cancer and the maintenance of bone integrity.

Public Health Relevance

Public Health: The constellation of clinical, epidemiologic and genetic factors will be used to generate an index of risk for the likelihood of developing osteonecrosis of the jaw (ONJ). Patients, dentists and medical oncologists will benefit from an instrument that will provide a personalized ONJ risk assessment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DE020197-04
Application #
8259041
Study Section
Subcommittee G - Education (NCI)
Program Officer
King, Lynn M
Project Start
2009-05-10
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
4
Fiscal Year
2012
Total Cost
$133,920
Indirect Cost
$9,920
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Choksi, Palak; Williams, Margaret; Clark, Patricia M et al. (2013) Skeletal manifestations of treatment of breast cancer. Curr Osteoporos Rep 11:319-28
Taichman, L Susan; Havens, Aaron M; Van Poznak, Catherine H (2013) Potential implications of adjuvant endocrine therapy for the oral health of postmenopausal women with breast cancer. Breast Cancer Res Treat 137:23-32
Rae, James M; Regan, Meredith M; Thibert, Jacklyn N et al. (2013) Concordance between CYP2D6 genotypes obtained from tumor-derived and germline DNA. J Natl Cancer Inst 105:1332-4
Bosch-Barrera, Joaquim; Merajver, Sofia D; Menendez, Javier A et al. (2011) Direct antitumour activity of zoledronic acid: preclinical and clinical data. Clin Transl Oncol 13:148-55
Van Poznak, C (2011) Making a case for defining osteonecrosis of the jaw. J Dent Res 90:399-401
Yamashita, Junro; McCauley, Laurie K; Van Poznak, Catherine (2010) Updates on osteonecrosis of the jaw. Curr Opin Support Palliat Care 4:200-6
Van Poznak, Catherine (2010) Osteonecrosis of the jaw and bevacizumab therapy. Breast Cancer Res Treat 122:189-91