New Agents for Taxol-Resistant Ovarian Carcinoma
Abstract
In this proposal, we will first test the ability of poly(L-glutamic acid)-paclitaxel (PG- TXL) to overcome certain types of Taxol-resistance controlled by P-gp l7O and HER-2/neu. We will also create and evaluate another novel generation of these polymeric formulations, HA-TXL, designed to selectively target and kill ovarian cancer cells that have high levels of CD44, a receptor for hyaluronic acid (HA) . This should facilitate efficient and specific receptor-mediated uptake of HA-TXL via its HA backbone. Our results to date indicate that PGA-TXL at a single-dose of 180 mg/kg (paclitaxel equivalents) injected i.p. was able to induce marked tumor growth delay and even apparent cures in two orthotopic human ovarian adenocarcinoma xenograft models, HEY and NMP-l, whether administered two or seven days after tumor implantation. In contrast, a multiple- dose MTD (10 mg/kg) regimen of Taxol was without efficacy in either model when administered at seven days post-implantation; some increase in lifespan was observed in the HEY model when the Taxol regimen was initiated two days after tumor implantation. Limited studies demonstrated similar trends with i.v. administration, as well as with multiple-dose i.p. schedules of PGA-TXL. These studies will be extended to CD44(+) tumor models and the HA-TXL formulations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA412168
Entities
People
- Jim Klostergaard
Organizations
- The University of Texas MD Anderson Cancer Center