摘要
Aggressive malignancies are characterized by relatively uncontrolled cell proliferation making them especially reliant on topoisomerase enzymes to enable high rates of DNA replication and transcription.DNA topoisomerases resolve topological problems associated with DNA replication and other essential cellular processes involving DNA,such as transcription and recombination^([1]).As such,they are important targets for anti-cancer therapeutics.Further,understanding of topoisomerase biology is important for unraveling the mechanistic basis for resistance to many widely used anti-cancer drugs,such as doxorubicin,etoposide,and topotecan,for which DNA topoisomerases are established targets.Interestingly,several drugs that are not considered to directly target topoisomerase enzymes,such as the nucleoside analogs 5-FU and AraC,and those in development such as the polymeric fluoropyrimidine CF10^([2]),also affect the function of topoisomerases.
基金
van Waardenburg RCAM in part funded by American Cancer Society UAB ACS-IRG Junior Faculty Development Grant(ACS-IRG-60-001-53)
Department of Defense OCRP pilot award W81XWH-15-1-0198
the National Institutes of Health Cancer Center Core Support Grant(P30CA013148)
National Institutes of Health-National Institute of Disorders and Stroke(1R21NS116312-01A1)
Gmeiner WH in part supported by the National Cancer Institute Cancer Center Support Grant(P30CA012197)issued to the Wake Forest Baptist Comprehensive Cancer Center and National Institutes of Health-National Cancer Institute R21 CA218933.
