Drug transporters of platinum-based anticancer agents and their clinical significance
Platinum-based drugs are among the most active anticancer agents and are successfully used in a wide variety of human malignancies. However, acquired and/or intrinsic resistance still represent a major limitation. Lately, in particular mechanisms leading to impaired uptake and/or decreased cellular accumulation of platinum compounds have attracted attention. In this review, we focus on the role of active platinum uptake and efflux systems as determinants of platinum sensitivity and -resistance and their contribution to platinum pharmacokinetics (PK) and pharmacodynamics (PD). First, the three mostly used platinum-based anticancer agents as well as the most promising novel platinum compounds in development are put into clinical perspective. Next, we describe the presently known potential platinum transporters - with special emphasis on organic cation transporters (OCTs) - and discuss their role on clinical outcome (i.e. efficacy and adverse events) of platinum-based chemotherapy. In addition, transporter-mediated tumour resistance, the impact of potential platinum transporter-mediated drug-drug interactions, and the role of drug transporters in the renal elimination of platinum compounds are discussed.
|Keywords||Cimetidine, Drug transporters, Metformin, Organic cation transporters (OCTs), PK resistance, Platinum, Solute carriers (SLCs)|
|Persistent URL||dx.doi.org/10.1016/j.drup.2010.12.002, hdl.handle.net/1765/34319|
Burger, H., Loos, W.J., Eechoute, K., Verweij, J., Mathijssen, A.H.J., & Wiemer, E.A.C.. (2011). Drug transporters of platinum-based anticancer agents and their clinical significance. Drug Resistance Updates, 14(1), 22–34. doi:10.1016/j.drup.2010.12.002