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Improved therapy of lung cancer

Institution: California Pacific Medical Center Research Institute
Investigator(s): Li-Xi Yang, M.D., Ph.D.
Award Cycle: 2000 (Cycle 9) Grant #: 9RT-0172 Award: $668,814
Subject Area: Cancer
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Taxol is a new anticancer drug developed in the 1990s for treatment of human cancers, including lung cancer. However, toxic side effects such as neutropenia (loss of white blood cells) and hypersensitivity reactions have limited the usefulness of this drug. We are seeking to develop and test a novel second-generation version of taxol that is more effective in killing human lung cancer cells as a radiation enhancement agent but less toxic to normal tissues. A new second-generation analog of taxol has been synthesized and found to be about 100 times more effective against lung cancer cells in vitro, and 100% curative effects on mammary tumors in animal models, in contrast to the parent drug taxol. Moreover, the analog is significantly less toxic in animal studies than the parent drug taxol.

We plan to test this promising analog on two human lung cancers using animal models, and to evaluate its therapeutic efficacy at clinically relevant doses for future application in human lung cancer therapy. In these studies its drug effects will be evaluated alone and in combination with radiotherapy, compared to those of taxol. These preclinical studies of this nature are complex and laborious, but they provide essential information on therapeutic properties of the taxol analog under clinically relevant conditions. Based on preliminary results it is hoped that this novel taxol analog will be superior to taxol, providing a unique combination of improved therapeutic action in killing lung cancer cells without any penalty in the form of increased drug toxicity. If therapeutic effects similar to those noted in tissue culture and in animal studies could be achieved on human lung cancers, the clinical benefits could be substantial.

Therefore, the development of newly synthesized second-generation taxol analogs with higher efficacy and reduced toxicity holds considerable promise for dramatically improved therapy of lung cancers. The proposed studies in this project will directly contribute to the design of clinical trials and to the development of a novel taxol analog as a clinically useful therapeutic agent for treating lung cancer.
Publications

Centrosomes-their role in tumors and cancer therapy.
Periodical: Anticancer Research Index Medicus:
Authors: Ro S, Yang LX ART
Yr: 2004 Vol: 24 Nbr: Abs: Pg: