Therapeutic targets for polycystic kidney disease.
BACKGROUND
Polycystic kidney disease (PKD) is a common genetic disease in which renal enlargement and loss of function is caused by progressive expansion of tubular cysts. To reverse the detrimental effects of PKD gene mutation(s) and to slow cystic expansion, new drug therapies are required.


METHODS
The underlying cell biology leading to identification of molecular targets for PKD is reviewed. Specific focus is on studies published at the early pre-clinical level. These include genetic and epigenetic modulators, and drugs to slow cystic expansion and disease progression. Discussion of specific drugs and clinical trials is not within the scope of this article. Literature research methods included EndNote and PubMed online searches using keyword combinations: polycystic kidneys disease, pre-clinical, molecular targets, signal transduction, genetic modulators, epigenetic, therapeutic, receptors, kinases. Where possible, the most recent citations concerning a given target are referenced.


CONCLUSIONS
It is suggested that the most promising targets for future therapeutic development are those that target upstream signaling events at cell membranes, such as the vasopressin-2 receptor (AVPR2), EGFR/ErbB2, and the β-1-integrin receptor, as well as the intracellular integrator kinase, c-Src.
a University College of London, Royal Free Hospital, UCL Centre for Nephrology , Rowland Hill Street, London, NW3 2PF, UK.
Patricia D
PD
Wilson
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D018450:Disease Progression; D015195:Drug Design; D044127:Epigenesis, Genetic; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D007690:Polycystic Kidney Diseases / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects
EGFR; G –protein; calcium; cyclic AMP; integrin; kinases; mechanosensation; polycystins; receptors