Grants and Contracts Details
Description
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.
Status | Finished |
---|---|
Effective start/end date | 7/1/02 → 6/30/05 |
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.