title: To kill or not to kill, that is the question: cytocidal antimalarial drug resistance.
abstract: Elucidating mechanisms of antimalarial drug resistance accelerates development of improved diagnostics and the design of new, effective malaria therapy. Recently, several studies have emphasized that chloroquine (CQ) resistance (CQR) can be quantified in two very distinct ways, depending on whether sensitivity to the growth inhibitory effects or parasite-kill effects of the drug are being measured. It is now clear that these cytostatic and cytocidal CQR phenotypes are not equivalent, and recent genetic, cell biological, and biophysical evidence suggests how the molecular mechanisms may overlap. These conclusions have important implications for elucidating other drug resistance phenomena and emphasize new concepts that are essential for the development of new drug therapy.
authors: Department of Chemistry, Georgetown University, 37th and O Streets NW, Washington DC 20057, USA; Department of Biochemistry and Cellular and Molecular Biology, Georgetown University, 37th and O Streets NW, Washington DC 20057, USA. Electronic address: roepep@georgetown.edu.
authors: Paul D
authors: PD
authors: Roepe
mesh_terms: D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology; D055808:Drug Discovery / Q000639:trends; D004351:Drug Resistance; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism; D057900:Transcytosis / Q000187:drug effects
chemical_list: D000962:Antimalarials; D002738:Chloroquine
keywords: Plasmodium falciparum; QTL analysis; autophagy; cytostatic; drug transport