MEMBRANES AND MEMBRANE TRANSPORT

This is proposal for support for a FASEB Summer Research Conference on Membranes and Membrane Transport Phenomena in Neoplasia. Membrane transport of anti-cancer agents has been a very important but often elusive aspect of cancer pharmacology. Since most drugs act on targets within cells, membrane transport is a requisite for drug action. Hence, transport has been shown to be a critical element in drug cytotoxicity and a key factor in acquired and natural drug resistance. An area of recent interest is in the role of membrane transport in pleiotropic drug resistance involving several classes of agents. Despite the importance of membrane transport in drug action, however, little is known about transport properties for highly potent drugs such as the antracyclines and the mechanisms by which membrane transport alterations result in reduced cellular uptake of drugs in the pleiotropic drug resistance phenomenon. One factor that limits progress in studies on membrane transport of anti-cancer drugs is the lack of involvement of physiologists and biophysicists who have as a primary interest basic aspects of transport processes. This FASEB Conference is designed to bring together investigators with a primary interest in the membrane transport of anti-cancer drugs and the role of cell membranes in the neoplastic process with investigators who have a primary interest in basic aspects of membrane phenomena-kinetics, thermodynamics, transduction processes and molecular biology. Critical issues in the transport of anti-cancer drugs will be addressed within the context of state of the art lectures on basic processes that involve the cell membrane. There will be considerable focus on the role of cell membranes in the transcuction of signals initiated at the cell surface and the relationship of these events to cell transformation and differentiation. The conference will consider cytotoxic nucleosides, antifolates and the pleiotropic drug resistance problem. The role of membrane transport as a determinent of drug action will be explored. Cloning of membrane transport carrier genes will be reviewed and extrapolation to studies to identify genes for anti-cancer drug carriers will be considered. We hope to attract the attention of the broader "transport and membrane community" to problems in anti-cancer drug transport and other issues that relate to the role of the cell membrane in neoplastic processes.