This Laboratory Program determines how good the discovery of new anticancer agents is and develops the candidate agent. In this project, decisions are made to: move the agent toward clinical development; carry out further analog search and synthesis efforts to find superior analogs; or, drop the agent from further consideration. In order to be entered into this project, the agent must be selectively cytotoxic for a solid tumor compared to the leukemia or normal cell in vitro. In addition, the agent must also be active in vivo (T/C less than or equal to 42%) against that same tumor. In this project, the following series of in vivo tests are carried out: (a) breadth of activity against a variety of solid tumors of mouse and human origin, including multidrug resistant (MDR) tumors; (b) optimal schedule determination, which includes identifying the schedule category; (c) acute and chronic patterns of toxicity assessment and host recovery time from maximum tolerated dosages; (d) cross-resistance patterns with selected standard agents. For an active series, """"""""head-to-head"""""""" analog comparison trials will be carried out in vivo, against selected tumors, and in the in vitro against a wide variety of tumors and normal cells. Also tumor model development and characterization will continue. All of these studies are planned to evaluate the following Central Hypothesis that the selective cytotoxicity for solid tumor cells in culture (compared to leukemias or normal cells) in the primary in vitro assays will predict for in vivo efficacy against the same tumors, as well as other solid tumors, and eventually human solid tumors in humans.
| Cruz-Rivera, Edwin; Friedlander, Michael (2011) Feeding preferences of mesograzers on aquacultured Gracilaria and sympatric algae. Aquaculture 322:218-222 |
| Boinpally, Ramesh R; Polin, Lisa; Zhou, Sen-Lin et al. (2003) Pharmacokinetics and tissue distribution of cryptophycin 52 (C-52) epoxide and cryptophycin 55 (C-55) chlorohydrin in mice with subcutaneous tumors. Cancer Chemother Pharmacol 52:25-33 |
