Greg Kucera Lab

Drug-Induced Cytotoxicity in Neoplastic Cells

The general aim of my laboratory's research is to influence the potential for clinical trials through laboratory investigations of anticancer drugs or combinations of anticancer drugs that affect cellular proliferation through signaling pathways. In addition, the lab is interested in the synthesis and testing of novel chemotherapeutic agents that potentially have dual mechanisms of action and can overcome drug resistance in order to maximize tumor cell cytotoxicity. These new chemical entities are constructed by combining synthetic lipid molecules with chemotherapy agents. The goal is to improve the efficacy of the chemotherapy agent by increasing the bioavailability of the agent. In addition, the selection of the synthetic lipid carrier is important not only for the delivery of the chemotherapeutic agent but also for the modulation of signaling pathways specific for enhancing the activity of the chemotherapeutic agent.

Our research has shown that conjugation of small molecular weight compounds to synthetic phospholipids increases the half-life of the active drug moiety, decreases toxic side effects, delivers more active drug to diseased sites, and allows for the entry of drug into the CNS and lymphoid tissues. Furthermore, because of the specific nature of the synthetic phospholipid carrier molecules the prodrug conjugates can be given orally and they are only activated intracellularly. The results obtained from these laboratory investigations will be ushered into clinical pharmacologic studies and into clinical trials in patients with malignant disease.