Cellular Pharmacology of Antineoplastic Drugs

Studies currently focus on identifying cellular targets which account for the sensitivity/resistance of different neoplastic histiotypes to the drug under study; such investigations are designed to elucidate key factors involved in drug response. Identification of a specific drug target will facilitate development of assays to both aid in selection of an appropriate population of patients for clinical trial based on the presence/absence of the target and to quantitate the therapeutic response in vitro. Currently ongoing investigations are focused on the novel anti-leukemic drug KRN5500 ,its apparent function as an analog of ceramide and its metabolism by the enzyme ceramidase. Additionally, efforts currently are being directed towards examination of a series of compounds reputed to block the binding of the Growth Factor Receptor Binding Protein-2 (GRB-2) to the onco protein bcr-abl. The disruption of this receptor-adaptor protein interaction may lead to abrogation of critical Ras-mediated downstream events in a manner similar to STI-571.

Recent Publications

NCBI PubMed listing of publications by David Vistica.

Kamishohara, M., Kenney, S., Domergue, R., Vistica, D.T., Sausville, E.A. Selective accumulation of the endoplasmic reticulum-Golgi intermediate compartment induced by the antitumor drug KRN5500.
Exp Cell Res. 2000 May 1;256(2):468-79.

Rivera, M.I., Stinson, S.F., Vistica, D.T., Jorden, J.L., Kenney, S., Sausville, E.A. Selective toxicity of the tricyclic thiophene NSC 652287 in renal carcinoma cell lines: differential accumulation and metabolism. Biochem Pharmacol 57(11): 1283-95, 1999.

Sriram, K., Boyd, M.R., Vistica, D.T., Ravindranath, R. In vitro neurotoxicity of the antitumor agent 9-methoxy-N2-methylelliipticinium acetate (MMEA): role of brain cytochrome P-450. Neurotoxicology 18(1): 97-104, 1997.

Shankar, L., Ravindranath, V., Boyd, M.R., Vistica, D.T., Shankar, S.K. Histological, histochemical and autoradiographic evidence of in vitro neurotoxic effects of the novel antitumor agent, 9-methoxy-N2-methylellipticinium acetate. Neurotoxicology 18(1): 89-95, 1997.

Vistica, D.T., Kenney, S., Hursey, M., Boyd, M.R. Role of membrane potential in the accumulation of quarternized ellipticines by human tumor cell lines. J Pharmacol Exp Ther 279(2): 1018-25, 1996.