Grants and Contracts Details
Intracellular drug accumulation is a critical determinant of cellular sensitivity to anticancer agents, and intracellular drug accumulation is regulated by membrane-associated drug transporters. Therefore, we hypothesize that drug transporters themselves can be considered as targets for lung cancer therapy, by identifying both the transporters highly expressed in lung cancer and the anticancer drugs that are substrates for those transporters. Genomic data has revealed dozens of drug transport genes, each of which might contribute to the uptake of anticancer drugs. To begin to target these transporters for lung cancer therapy, we have measured the RNA levels of over 20 OAT, organic cation transporter (OCT), and nucIeoside/nucIeobase transporter genes in 5 lung cancer cell lines. Preliminary data from these studies demonstrate some of these drug transport genes are over-expressed in lung cancer cell lines, making these transport genes potential targets for novel lung cancer therapy. This is significant since we have found that a transport gene overexpressed in leukemia cell lines is also over-expressed in leukemic blasts from patients. Preliminary data has also demonstrated that we can successfully identify anticancer drugs that are substrates for transport genes. The specific aim of this study is to apply this paradigm to the potential therapy of lung cancer, by identifying drug transport genes highly expressed in lung tumors, and to identify anticancer drug substrates for these transporters. This will be accomplished by measuring RNA levels of approximately 40 transport genes in lung tumors, and to then to use gene transfection studies to confirm functional relationships between anticancer drugs and transporters over-expressed in lung cancer. These studies will give us the necessary preliminary data we need to focus future grant applications on specific proposals for novel therapeutic approaches for lung cancer.
|Effective start/end date||7/1/02 → 6/30/05|
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