A Fresh Approach to Treating Cancer: Targeting Proteins

(DGIwire) – Many headlines from the world of cancer research are focusing on the potential of checkpoint inhibitors—a way of releasing the brakes on immune cells so they can attack cancer cells. But as recently noted on LifeScienceLeader.com, some companies are exploring drugs that could work in combination with checkpoint inhibitors in the hopes of having a greater effect.

“One approach that appears fruitful is to study drugs targeting particular proteins that are almost exclusively expressed in cancer cells,” says Douglas J. Swirsky, President and CEO of Rexahn Pharmaceuticals. “Each of the candidates we are studying explores a unique mechanism.”

Rexahn is studying its proprietary compound RX-3117 in pancreatic cancer and advanced bladder cancer, and another compound, RX-5902, in triple negative breast cancer. The company believes there is a strong possibility that these may show positive effects when administered to patients especially in combination with immunotherapy or chemotherapy. 

Broadly, RX-3117—which has been granted orphan drug designation—can bind with an activation enzyme found mainly in cancer cells. Once activated, this compound travels into a cancer cell’s nucleus where it is incorporated into the DNA and RNA, resulting in the cell’s death. This approach differs from traditional chemotherapy, which non-selectively kills both cancer cells and normal healthy tissue in the body. Studies to date indicated that in addition to killing cancer cells while leaving healthy cells intact, RX-3117 has shown few severe adverse events and allows oral dosing. It may also be able to work in tandem with existing therapies and facilitate a spectrum of anticancer activity.

RX-3117 is being evaluated in combination with a chemotherapeutic drug in patients with metastatic pancreatic cancer. Preliminary data from the first 24 patients in the study show that RX-3117 is safe and well-tolerated. One patient experienced a complete response after six months of therapy; eight patients exhibited a partial response; and a further 13 patients had stable disease. The overall response rate was 38 percent and the disease stabilization rate at eight weeks was 92 percent.

Meanwhile, RX-5902 binds to a key protein that is also found primarily in tumor cells and only in very small amounts in normal tissue. By doing so, RX-5902 turns off cancer genes, resulting in a decrease in cancer cell growth and metastases, and an increase in the body’s immune system’s ability to fight cancer. Preliminary data from a triple negative breast cancer study in patients whose cancer had progressed after multiple prior treatments showed encouraging responses, with two patients showing stable disease for longer than 200 days. Notably, one subject—a 78-year-old woman with malignant neoplasm of the right breast who had progressed on all of her previous therapies—showed an overall tumor reduction of more than 18 percent.

“Further work will shed light on the extent to which these therapies could potentially play a useful role in combination with existing approaches,” Swirsky adds.