Therapeutics in renal disease: the road ahead for antiproliferative targets.
Discovery into the molecular basis of renal disease is occurring at an unprecedented rate. With the advent of the NIH Roadmap, there is a greater expectation of translating this knowledge into new treatments. Here, we review the therapeutic strategy to preserve renal function in proliferative renal diseases by directly inhibiting the mitogenic pathways within renal parenchymal cells that promote G0 to G1/S cell-cycle phase progression. Reductionist methodologies have identified several antiproliferative molecular targets, and promising preclinical testing of leading small-molecule drugs to modulate these targets has now led to landmark clinical trials. Yet, this advancement into targeted therapy highlights important differences between the therapeutic goals of molecular nephrology versus molecular oncology and, by extension, the poorly understood role of alternative target activity in drug efficacy. Systems research to clarify these issues should accelerate the development of this promising therapeutic strategy.
Nelson
Peter J
PJ
Division of Nephrology, New York University School of Medicine, New York, NY 10016, USA. nelsop02@popmail.med.nyu.edu
Shankland
Stuart J
SJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001806:Blood Urea Nitrogen; D002455:Cell Division / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D006427:Hemin; D051547:Heme Oxygenase-1