Discovery links cellular structures to kidney cancer treatment outcomes

When fighting cancer, some patients may respond well to certain treatments, while others might not be as fortunate, with little explanation as to why. Now, in new research fom the Perelman School of Medicine, Shelley Berger, the Daniel S. Och University Professor and director of Penn's Epigenetics Institute, and Katherine Alexander, an assistant professor at Cold Spring Harbor Laboratory, have found a possible source of this variability in clear cell renal cell carcinoma (ccRCC)-the most common kidney cancer diagnosed in adults. The findings of their study are published in Nature Cell Biology.

The research finds that kidney tumors have two different patterns of cellular structures known as nuclear speckles. The research, conducted in Berger's lab at Penn, shows a potential correlation between speckle patterns and patient outcomes. Berger and Alexander collaborated with Celeste Simon, Arthur H. Rubenstein Professor of Cell and Developmental Biology and scientific director of the Abramson Family Cancer Research Institute at Penn.

"We found if a patient has a normal or abnormal speckle arrangement, they might be more responsive to one drug versus another. Of course, more research needs to be done," explains Alexander, who completed her postdoctoral fellowship in Berger's lab.

Discovered more than 100 years ago, nuclear speckles are tiny cellular structures that reside in the nucleus. These speckles intermingle with DNA and help regulate gene activity. This newly published research reveals that nuclear speckles have two different signatures in ccRCC: normal-like and aberrant. Normal speckles tend to congregate toward the center of the nucleus; aberrant speckles are more dispersed.

"How these signatures affect patient outcomes remains a mystery for now," Berger says. "However, the search for answers may lead to more personalized treatments. This discovery offers a new starting point in ccRCC."

"It's the first suggestion that this would be potentially applicable to giving someone [diagnosed with ccRCC] one drug or another. That's huge because cancer therapy has a lot of horrible side effects," says Alexander. "To be able to tell a patient, 'Your tumor looks like this, so we think this drug will work better than this drug,' is something we really need."

This story is by Matt Toal. Read more at Penn Medicine News.