Modeling Neoplastic Growth in Renal Cell Carcinoma and Polycystic Kidney Disease

Renal cell carcinoma (RCC) and autosomal dominant polycystic kidney disease (ADPKD) share several characteristics, including neoplastic cell growth, kidney cysts, and limited therapeutics. As well, both exhibit impaired vasculature and compensatory VEGF activation of angiogenesis. The PI3K/AKT/mTOR and Ras/Raf/ERK pathways play important roles in regulating cystic and tumor cell proliferation and growth. Both RCC and ADPKD result in hypoxia, where HIF-alpha signaling is activated in response to oxygen deprivation. Primary cilia and altered cell metabolism may play a role in disease progression. Non-coding RNAs may regulate RCC carcinogenesis and ADPKD through their varied effects. Drosophila exhibits remarkable conservation of the pathways involved in RCC and ADPKD. Here, we review the progress towards understanding disease mechanisms, partially overlapping cellular and molecular dysfunctions in RCC and ADPKD and reflect on the potential for the agile Drosophila genetic model to accelerate discovery science, address unresolved mechanistic aspects of these diseases, and perform rapid pharmacological screens.

Automated summary

RCC and ADPKD share similarities in tumor cell growth, cyst formation, and angiogenesis, with involvement of pathways like PI3K/AKT/mTOR and Ras/Raf/ERK. Hypoxia triggers HIF-alpha activation, potentially involving primary cilia and altered cell metabolism in disease progression. Drosophila model shows potential for accelerating disease mechanism understanding and drug screening.