The purpose of this K23 proposal is to consolidate the investigator's diverse training experiences into an independent research program that identifies and develops genetic and clinical biomarkers for the individualized management of cancer therapeutics. To accomplish this, Dr. Maitland will: 1) complete additional didactic and tutorial education in pharmacometrics, statistical genetics, and multivariate analysis, 2) be primarily mentored by Dr. Mark Ratain (an internationally recognized expert in both early stage cancer drug development and inter-individual variability in cancer therapeutics) in the design, execution, and interpretation of studies to identify biomarkers for inhibition of the Vascular Endothelial Growth Factor (VEGF) Signaling Pathway (VSP), and 3) be mentored by senior colleagues in the Oncology and Human Genetics Sections of the University of Chicago Biological Sciences Division on relevant genetic analyses, and design and execution of a multi-center study to test the utility of the most promising of the developed biomarkers for inhibition of the VSP. VSP inhibitors constitute a new class of anticancer agents that modify the vasculature and may thereby enhance the efficacy of concurrent chemotherapy. Reliable biomarkers for VSP inhibition do not yet exist but would guide the optimal dosing and selection of VSP inhibitors for a specific patient. To identify and develop such biomarkers the investigator will: 1 Characterize the relationship between the VSP inhibitor sorafenib and blood pressure, and determine the pharmacological basis for interindividual variability in blood pressure response, 2) test candidate gene polymorphisms and clinical variables for contribution to this variability and the relevance of blood pressure variability to treatment response, and 3) test the effects of typical anticancer interventions on serum concentrations of the endothelial cell-synthesized molecule angiopoietin-2(Ang2), determine the intrinsic variables affecting serum concentrations of Ang2, and identify Quantitative Trait Loci (sites for candidate gene variants associated with serum concentrations of Ang2). Relevance: New drugs, and new technologies to guide their use, offer the possibility for physicians to tailor treatment for the specific patient. This """"""""personalized medicine"""""""" promises safer, more effective treatment for patients with cancer. This grant will help train Dr. Maitland to be an expert in the conduct of clinical and laboratory studies for personalized cancer medicine.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RTRB-L (M3))
Program Officer
Lim, Susan E
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Chicago
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Li, C H; Bies, R R; Wang, Y et al. (2016) Comparative Effects of CT Imaging Measurement on RECIST End Points and Tumor Growth Kinetics Modeling. Clin Transl Sci 9:43-50
Maitland, Michael L; Xu, Chun-Fang; Cheng, Yu-Ching et al. (2015) Identification of a variant in KDR associated with serum VEGFR2 and pharmacodynamics of Pazopanib. Clin Cancer Res 21:365-72
O'Donnell, Peter H; Karovic, Sanja; Karrison, Theodore G et al. (2015) Serum C-Telopeptide Collagen Crosslinks and Plasma Soluble VEGFR2 as Pharmacodynamic Biomarkers in a Trial of Sequentially Administered Sunitinib and Cilengitide. Clin Cancer Res 21:5092-9
Karovic, S; Wen, Y; Karrison, T G et al. (2014) Sorafenib dose escalation is not uniformly associated with blood pressure elevations in normotensive patients with advanced malignancies. Clin Pharmacol Ther 96:27-35
Thomeas, Vasiliki; Chow, Selina; Gutierrez, Jose O et al. (2014) Technical considerations in the development of circulating peptides as pharmacodynamic biomarkers for angiogenesis inhibitors. J Clin Pharmacol 54:682-7
Müller, Peter; Quintana, Fernando A; Rosner, Gary L et al. (2014) Bayesian inference for longitudinal data with non-parametric treatment effects. Biostatistics 15:341-52
Maitland, M L; Wu, K; Sharma, M R et al. (2013) Estimation of renal cell carcinoma treatment effects from disease progression modeling. Clin Pharmacol Ther 93:345-51
Wheeler, Heather E; Maitland, Michael L; Dolan, M Eileen et al. (2013) Cancer pharmacogenomics: strategies and challenges. Nat Rev Genet 14:23-34
Bhatta, Sumita S; Wroblewski, Kristen E; Agarwal, Kelly L et al. (2013) Effects of vascular endothelial growth factor signaling inhibition on human erythropoiesis. Oncologist 18:965-70
Sharma, M R; Maitland, M L; Ratain, M J (2012) Models of excellence: improving oncology drug development. Clin Pharmacol Ther 92:548-50

Showing the most recent 10 out of 22 publications