GI Translational Research Lab

Main Research Focus:
Dr. Eckhardt's lab is part of the multiple-PI lab that is involved in developmental therapeutics and translational studies related to GI cancers. In addition to conducting correlative biological assays for some of our Phase I clinical trials, a major focus of our lab is the development of predictive and pharmacodynamic biomarkers for novel, molecularly-targeted anticancer agents. The current focus in on VEGF-R, mek, IGF-1R, HDAC, and aurora kinase inhibitors. The model systems we are developing and characterizing include cell lines, colorectal (CRC) stem cells, 3-D cultures, orthotopic and metastatic models, and GI human tumor explant models. In collaboration with Dr. Natalie Serkova, we are interested in preclinical imaging using micro-CT/PET, DCE-MRI, as well as metabolomics. Our funding comes from the NCI, the pharmaceutical industry, and private foundations.

Recent Publications

1. Morelli MP, Cascone T, Troiani T, Tuccillo C, Bianco R, Normanno N, Romano M, Veneziani BM, Fontanini G, Eckhardt SG, De Pacido S, Tortora G, Ciardiello F. Anti-tumor activity of the combination of cetuximab, an anti-EGFR blocking monoclonal antibody and ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinases. J Cell Physiol 208(2):344-53, 2006

2. Teresa Troiani, Owen Lockerbie, Mark Morrow, Fortunato Ciardiello, S.Gail Eckhardt. Sequence-Dependent Inhibition of Human Colon Cancer Cell Growth and of Pro-Survival Pathways by Oxaliplatin in combination with ZD6474 (ZACTIMA™), an inhibitor of VEGFR and EGFR Tyrosine Kinases Molecular Cancer Therapeutics 5(7):1883-94, 2006.

3. Messersmith WA, Hidalgo M, Carducci M, Eckhardt SG. Novel targets in solid tumors: MEK inhibitors. Clin Adv Hematol Oncol 4(11):831-6, 2006.

4. Medeiros BC, Landau HJ, Morrow M, Lockerbie RO, Pitts T, Eckhardt SG. The farnesyl transferase inhibitor, tipifarnib, is a potent inhibitor of the MDR1 gene product, P-glycoprotein, and demonstrates significant cytotoxic synergism against human leukemia cell lines. Leukemia Apr; 21(4):739-46, 2007.

5. S. Hariharan, D. Gustafson, S. Holden, D. McConkey, D. Davis, M. Morrow, M. Basche, L. Gore, C. Zang, C. L. O’Bryant, A. Baron, D. Gallemann, D. Colevas & SG Eckhardt. Assessment of the biological and pharmacological effects of the Integrin Receptor Antagonist, cilengitide (EMD 121974), in patients with advanced solid tumors. Ann Oncol (In Press), 2007.

6. Bradshaw-Pierce EL, Eckhardt SG, Gustafson DL. A physiologically based pharmacokinetic model of docetaxel disposition: from mouse to man. Clin Cancer Res May 1;13(9):2768-76, 2007.

7. Teresa Troiani, Natalie J. Serkova, Daniel L. Gustafson, Thomas K. Henthorn, Owen Lockerbie, Andrea Merz, Michael Long, Mark Morrow, Fortunato Ciardiello, S.Gail Eckhardt. Investigation of Two Dosing Schedules of Vandetanib (ZD6474), an Inhibitor of VEGFR and EGFR Signaling, in Combination with Irinotecan in a Human Colon Cancer Xenograft Model. Clin Cancer Res 13(21): 6450-6458, 2007.

8. Serkova NJ, Spratlin JL, Eckhardt SG. NMR-based metabolomics: Translational application and treatment of cancer. Curr Opin Mol Ther 9(6):572-85, 2007.

9. Alex A Adjei, Roger B Cohen, Wilbur Franklin, Clive Morris, David Wilson, Julian R Molina, Lorelei J Hanson, Lia Gore, Laura Chow, Stephen Leong, Lara Maloney, Gilad Gordon, Heidi Simmons, Allison Marlow, Kevin Litwiler, Suzy Brown, Gregory Poch, Katie Kane, Jerry Haney, and S. Gail Eckhardt. A Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral, Small-Molecule MEK1/2 Inhibitor AZD6244 (ARRY-142886) in Patients with Advanced Cancers. J Clin Oncol, (in press), 2007.

Lab Personnel

Todd Pitts, M.S. - Professional Research Associate and Laboratory Manager
John Tentler, Ph.D. - Assistant Professor of Medicine/Oncology
Amy Meyer, Ph.D.- Instructor of Medicine/Oncology
Maria Pia Morelli, M.D. - Senior Research Fellow
Jennifer Spratlin, M.D. - Senior Research Fellow
Erica Bradshaw-Pierce, Ph.D. - Postdoctoral Fellow
Sujatha Nallapareddy, M.D. - Senior Research Fellow
Sara Kaufman, BA - Professional Research Assistant