Introduction: 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.
Areas covered: 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.
Expert opinion: 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.
Keywords: EGFR; G –protein; calcium; cyclic AMP; integrin; kinases; mechanosensation; polycystins; receptors.