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Edward A Sausville
 

Edward A Sausville M.D., Ph.D.

Academic Title: Professor
Primary Appointment: Medicine
Secondary Appointments: Pharmacology
Administrative Title: Interim Division Head
Additional Title(s): Interim Division Chief of Hematology/Oncology; Associate Director for Clinical Research, University of Maryland Marlene & Stewart Greenebaum Cancer Center
esausville@umm.edu
Location: UMH Room S9D07
Phone: (410) 328-7394
Fax: (410) 328-6896

Research Interests:

I am a Medical Oncologist and Pharmacologist who until 2004 was Associate Director of the National Cancer Institute’s Division of Cancer Treatment and Diagnosis for the Developmental Therapeutics Program. This Program directs the NCI’s preclinical anti-cancer drug development portfolio, from screening studies through formulation, manufacture, and safety testing for agents to enter clinical trial sponsored by NCI. My clinical research interests at U. Maryland are directed at early phase clinical trials of new drugs for cancer treatment. Active clinical protocols under my direction include: A Phase I Dose-Escalation Study of Intravenous 17-allylaminogeldanamycin (17-AAG) [NSC 330507, IND 57,966] and Oral Bay 43-9006[NSC 724772, IND #69,896] Administered in Patients with Pretreated Advanced Solid Tumors (sponsored by NCI); A Phase I Dose Escalation Safety Tolerance Study of PPI-2458 in Subjects with Non-Hodgkins Lymphoma or Solid Tumors (sponsored by Praecis Pharmacueticals); A Phase I, Open-Label, Dose Escalation Study to Evaluate the Safety Tolerability, and Pharmacokinetics of Weekly Intravenous INNO-105 in Adult Patients with Advanced Solid Malignancies (sponsored by Innovive); Phase I Study of EC145 Administered Weeks 1 and 3 of a 4 Week Cycle (sponsored by Endocyte) Under development is: A Phase I Study of AFP464 (aminoflavone prodrug) in Patients with Advanced Solid Tumors (NCI). My translational research interests at U. Maryland focus on developing pharmacodynamic endpoint assays for novel agents under development here. This is in collaboration with Dr. Angelika Burger, head of the Cancer Center’s Translational Core and an Associate Professor of Pahrmaciology & Experimental Therapeutics. We have recently demonstrated that geldanamycin substrate Heat Shock Protein 90 is secreted from tumor cells in an isoform-specific fashion, and this may allow it to be a marker for geldanamcyin function in patients. In addition, we have developed a potential assay for induction of DNA damage in aminoflavone-treated cells and tumors through induction of histone phosphorylation. I look forward to developing future assays for biologic effect of c ell cycle modulators for ultimate study in early phase clinical trials, and brining these to U Maryland.
 

Publications:

Burger AM, Fiebig HH, Stinson SF, Sausville EA.  17-(Allylamino)-17-demethoxygeldanamycin activity in human melanoma models. Anticancer Drugs, 15: 377-87; 2004.

Hollingshead M, Alley M, Burger AM, Borgel S, Pacula-Cox C, Fiebig HH, Sausville EA. In vivo antitumor efficacy of 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride), a water-soluble geldanamycin derivative. Cancer Chemother Pharmacol, 56(2): 115-25; 2005. [Epub 2005 Mar 25]

Smith V, Sausville EA, Camalier RF, Fiebig HH, Burger AM. Comparison of 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17DMAG) and 17-allylamino-17-demethoxygeldanamycin (17AAG) in vitro: effects on Hsp90 and client proteins in melanoma models. Cancer Chemother Pharmaco, 56(2): 126-37; 2005. [Epub 2005 Apr 20]

Ryan QC, Headlee D, Acharya M, Sparreboom A, Trepel JB, Ye J, Figg WD, Hwang K, Chung EJ, Murgo A, Melillo G, Elsayed Y, Monga M, Kalnitskiy M, Zwiebel J, Sausville EA. Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. J Clin Oncol, 23(17): 3912-22; 2005.

Fandy TE, Shankar S, Ross DD, Sausville EA, Srivastava RK. Interactive effects of HDAC inhibitors and TRAIL on apoptosis are associated with changes in mitochondrial functions and expressions of cell cycle regulatory genes in multiple myeloma. Neoplasia, 7(7): 646-57; 2005.

Chung EJ, Lee S, Sausville EA, Ryan Q, Karp JE, Gojo I, Telford WG, Lee MJ, Kong HS, Trepel JB. Histone deacetylase inhibitor pharmacodynamic analysis by multiparameter flow cytometry. Ann Clin Lab Sci, 35(4): 397-406; 2005.

Amornphimoltham P, Patel V, Sodhi A, Nikitakis NG, Sauk JJ, Sausville EA, Molinolo AA, Gutkind JS. Mammalian target of rapamycin, a molecular target in squamous cell carcinomas of the head and neck. Cancer Res, 65(21): 9953-61; 2005.

Van Waes C, Chang AA, Lebowitz PF, Druzgal CH, Chen Z, Elsayed YA, Sunwoo JB, Rudy SF, Morris JC, Mitchell JB, Camphausen K, Gius D, Adams J, Sausville EA, Conley BA. Inhibition of nuclear factor-kappaB and target genes during combined therapy with proteasome inhibitor bortezomib and reirradiation in patients with recurrent head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys., 63(5): 1400-12; 2005. [Epub 2005 Jul 11]

Shen Y, Xie Q, Norberg M, Sausville E, Vande Woude G, Wenkert D. Geldanamycin deerivative inhibtiorn of HGHF/SF mediated met tyurosine kinase receptor-dependent urokinase-plasminogen activation. Biorganic & Med Chem, 13(16): 4960-71; 2005.

Glaze ER, ambert AL, Smith AC, Page JG, Johnson WD, McCormick DL, Brown AP, Levine BS, Covey JM, Egorin MJ, Eiseman JL, Holleran JL, Sausville EA, Tomaszewski, JE. Preclinical toxicity of a geldanamycin analog, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), in rats and dogs: potential clinical relevance. Cancer Chemother Pharmacol., 56(6): 637-47; 2005. [Epub 2005 Jun 29]

Decker S, Sausville EA. Preclinical modeling of combination treatments: fantasy or requirement? Ann N Y Acad Sci., 1059: 61-9; 2005.

Acharya MR, Sparreboom A, Sausville EA, Conley BA, Doroshow JH, Venitz J, Figg WD. Interspecies differences in plasma protein binding of MS-275, a novel histone deacetylase inhibitor. Cancer Chemother Pharmacol, 57(3): 275-81; 2006. [Epub 2005 Jul 19]