Adenosine Triphosphate-Binding Cassette Proteins and Bioavailability: “We Can Pump You Up (or Out)”

Extract

The adenosine triphosphate-binding cassette (ABC) superfamily of proteins (1–8) has become a prominent and important area of research in antineoplastic pharmacology and tumor cell biology (9–13). The article by Jonker et al. (14) in this issue of the Journal is an excellent example of the careful types of studies being pursued in this ever-expanding area of research. Consideration of the results of this article and others like it raises fundamental issues and questions in a variety of areas almost as disparate as the various members of the ABC superfamily and the substrates they handle.

The fact that ABC proteins are inherent components of a wide range of cells and organisms should make it obvious that they were put there for a reason. Only oncologic hubris could lead one to the rather parochial opinion that these energy-dependent cellular pumps were created to produce cellular resistance to antineoplastic chemotherapy. The importance of these cellular constituents in maintenance of cellular homeostasis and tissue integrity and of protection from a wide variety of potentially damaging cellular and environmental compounds continues to be defined (1–7,15–18). This definition is occurring through ongoing identification of new members of this superfamily of proteins and demonstration of their unique, as well as overlapping, substrate specificities.