|Tamara Minko--Courtesy of Rutgers|
Ovarian cancer cells are known to form resistance over time to chemotherapy, limiting the effect that standard cancer drugs can have on the disease. And now, researchers at Rutgers University have developed an RNA method to attack rampant proteins causing the drug resistance, allowing chemotherapy to then take out the cells.
The protein CD44 has been shown to cause ovarian cancer to reach the more advanced stages by enabling cancer cells to metastasize and become more drug resistant, making them less likely to respond to the anticancer drugs alone. So the researchers used a small interfering RNA to knock down this protein and render the cancer cell more susceptible to the cancer drug paclitaxel.
Lead researcher Tamara Minko explained the process in an email to FierceDrugDelivery: "First, in addition to the anticancer drug (paclitaxel), the proposed developed complex therapeutic system contains a suppressor of drug resistance (siRNA targeted to CD44 protein; CD44 protein is mainly responsible for drug resistance in ovarian and some other types of cancer) that restore the sensitivity of cancer cells to the anticancer drug," she wrote. "Therefore, an increase in the dose of an anticancer drug is no longer required. Second, the system delivers active components specifically to cancer cells, limiting adverse side effects in healthy tissues. Third, the suppression of CD44 protein limits metastases."
But as almost a decade of research can suggest, delivering RNA molecules to the inside of a cell can be very difficult. The genetic compound is often too fragile to exist in the bloodstream and does not penetrate cancer cells, according to Minko, who worked with researcher Lorna Rodriguez. The nanoscale delivery system they used prevents the RNA from degrading in the blood stream and allows its internalization into the cells, she wrote.
In the study, Minko and Rodriguez isolated human ovarian cancer cells to induce the disease in mice, and they tested the nano-delivered RNA and paclitaxel on the animals. The whole system included a tumor-targeting hormone LHRH, the CD44-targeted siRNA and a polypropylenimine dendrimer to carry the components together, she said.
Minko and Rodriguez have filed a patent application and are raising money for clinical trials, Minko said.
"Once the ovarian cancer becomes drug resistant we cannot cure it," Rodriguez said in a report from Rutgers. "Circumventing the development of drug resistance is a reasonable approach and very much needed."
- here's the Rutgers report