Similarities Between Polycystic Kidney Disease, Cancer May Point to Future Therapeutic Options

PHILADELPHIA (April 16, 2015)— Researchers at Fox Chase Cancer Center recently conducted a review of the pathological features of a progressive inherited disease called autosomal dominant polycystic kidney disease (ADPKD). They found many similarities between ADPKD and cancer’s signaling pathways and inhibitors, highlighting potential avenues for the use of existing cancer therapeutics in the treatment of ADPKD.

The review was published in Nature Reviews Nephrology.

“As we learn more about molecular defects of disease and build really detailed ‘maps’ describing what goes wrong in cancer or chronic kidney disease or stroke, the more we realize that some specific cell signaling pathways are similarly affected, even though the gross manifestation of the disease at the organ level looks very different,” said Erica A. Golemis, PhD, deputy scientific director and co-chair of molecular therapeutics at Fox Chase Cancer Center. ADPKD is the most common inherited renal disease, affecting about 1 in 500 people. Starting in their twenties, individuals with ADPKD present with hypertension and other symptoms, and by middle age will develop a much more serious disease burden, including characteristically the development of fluid-filled renal cysts that destroy normal kidney function, culminating in end-stage renal disease that requires dialysis or transplant.

“By identifying common signaling defects, we may have the opportunity to take drugs developed for conditions affecting lots of patients, where there has been a huge investment in therapeutics, and use them to benefit patients suffering from conditions that are serious but affect fewer people—and hence have not attracted the same level of investment,” Dr. Golemis said.

In their review, Dr. Golemis and colleagues systematically compared ADPKD with the hallmarks of cancer— such as inducing angiogenesis or the presence of inflammation—and identified a surprising number of common signaling features between the two disease types.

According to Dr. Golemis, researchers have already begun mining available sets of drugs developed for heart disease and cancer to develop clinical trial concepts for ADPKD. One example is the use of angiotensin inhibitors such as lisinopril, developed to control high blood pressure.

“Conversely, by systematic comparison of ADPKD and cancer, and pinpointing areas where the two diseases differ, we can potentially gain insight into important mechanisms that are essential for the presentation of the disease,” Dr. Golemis said. “Despite many signaling similarities, ADPKD cells form cysts and ‘stay in place’; tumors invade and metastasize, contributing to the much greater lethality of cancer.”

In their review, the researchers also evaluated features of ADPKD and determined whether these same features exist in cancer cells.   

One element of cell signaling function that researchers find particularly provocative is the role of ciliary function. The cilium is a small organelle that stick outs of the cell surface and displays a receptor for certain types of cell signals. Cilia play an important role in the maintenance of normal kidney function.

There is growing evidence in ADPKD that the cilia need to be maintained to have the disease, whereas with cancers, the role of cilia seems to be split, with certain tumors types depending on the cilia for signaling whereas other types do not.

“These data show that it pays to look more broadly across disease types and not work in research silos,” Dr. Golemis said. “We have found that a similar set of genes is being used in different diseases in slightly different contexts, and we have reached a point where comparing signaling defects from one disease to another might allow us to develop ideas for new therapeutics.”