Laboratory prediction of clinical chemotherapeutic drug resistance: a working model exemplified by acute leukaemia.
Recent research into mechanisms of resistance to chemotherapy in acute leukaemia has been focused on various protective mechanisms at the cellular level, such as drug uptake, efflux, metabolism and DNA repair mechanisms, while therapeutic failures due to other potentially important causes have received relatively little attention. Here we describe a simple model to account for three major determinants of tumour response in acute leukaemia: cellular drug sensitivity, leukaemic cell regrowth potential and systemic drug exposure. Possible ways of measuring these parameters are discussed. It is suggested that laboratory estimation of these parameters may provide valuable information on clinical drug resistance and may help to design more adequate treatment strategies for the individual patient.
Larsson
R
R
Division of Clinical Pharmacology, University Hospital, Uppsala University, Sweden.
Nygren
P
P
D000208:Acute Disease; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008954:Models, Biological; D012008:Recurrence; D012074:Remission Induction