title: The role of impaired transport in (pre)clinical resistance to methotrexate: insights on new antifolates.
abstract: Impaired transport appears to be a common mechanism of resistance of neoplastic cells to the antifolate methotrexate. The extensive knowledge of the molecular, biochemical and functional properties of the membrane transport systems for folates, in particular the reduced folate carrier (RFC) and membrane folate receptors (MFR), has made an important contribution to the rational design of novel antifolates that are either more efficiently internalized via these transporters or can simply bypass these transport routes. The current status of exploiting the RFC and MFR for transport of novel antifolates active in preclinical model systems and a clinical setting will be reviewed, with a special reference to childhood acute lymphoblastic leukemia (ALL) and acute non-lymphoblastic leukemia (ANLL).
authors.affiliation: Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands. g.jansen@azvu.nl
authors.forename: G
authors.initials: G
authors.lastname: Jansen
authors.forename: R
authors.initials: R
authors.lastname: Pieters