Scientists slowed growth of ovarian tumors in mice using nanoparticles to deliver suicide genes

Scientists slowed growth of ovarian tumors in mice using nanoparticles to deliver suicide genes

Scientists in the US have found a way of slowing the growth of ovarian cancer tumors in mice by using nanoparticles to deliver suicide genes to the exact tumor location without damaging healthy cells. They hope a therapy using this method could be tested in humans within the next two years.

The study was the work of lead researcher Dr Janet Sawicki, a professor at the Lankenau Institute for Medical Research in Wynnewood, Pennsylvania, and colleagues and is published online in the 1 August issue of the journal Cancer Research.

Although early stage ovarian cancer can be treated with a combination of surgery and then chemotherapy, there are currently no effective treatments for patients with advanced ovarian cancer that recurs after surgery and primary chemotherapy, meaning that most relapse.

For the study Sawicki and colleagues at the Massachusetts Institute of Technology conducted preclinical tests in mice with primary and advanced ovarian cancer tumors.

First they measured the volume of the tumors and then they injected them with nanoparticles (these are less than one thousandth of the thickness of human hair) carrying a special type of suicide gene. Some mice were not injected (the controls).

More specifically, they used a "cationic biodegradable poly(beta-amino ester) polymer as a vector for nanoparticulate delivery of DNA encoding a diphtheria toxin suicide protein (DT-A)".

When they compared the volume of the tumors before and after treatment, they found that while the treated tumors had doubled in size, this was significantly less than what they found in the untreated mice: their tumors had increased to between four and six times their original size.

Also, four of the treated tumors didn't grow at all, while all the tumors in the control mice grew, they said.

They also found that giving the nanoparticle therapy to mice with three different types of ovarian cancer prolonged lifespan by nearly four weeks, suppressed tumor growth more effectively, and with minimal general toxic side effects, compared with mice treated with cisplatin and paclitaxel (a standard combination chemotherapy for women with advanced ovarian cancer).

Sawicki told the press that there was "reason to hope":

"We now have a potential new therapy for the treatment of advanced ovarian cancer that has promise for targeting tumor cells and leaving healthy cells healthy."

The study is striking because it appears to overcome a common problem in ovarian cancer research: how to hit the target accurately without damaging healthy tissue.

Dr Edward Sausville, an associate editor of Cancer Research and associate director for clinical research at the Greenebaum Cancer Center at the University of Maryland, said the study was remarkable because of the multiple ways the researchers show it's possible to target ovarian cancer cells.

They were able not only to deliver the toxin gene to the tumor site (in the peritoneum), but they were also able to selectively activate it inside the cancer cells.

"A real plus of a cancer therapy like this is not just the functionality of the nanoparticle construct molecule, but the ability to deliver the toxin to the tumor cells," said Sausville, who agreed with the authors' estimate that clinical trials in humans could be just 18 months away.

"Nanoparticle-Delivered Suicide Gene Therapy Effectively Reduces Ovarian Tumor Burden in Mice."

Yu-Hung Huang, Gregory T. Zugates, Weidan Peng, David Holtz, Charles Dunton, Jordan J. Green, Naushad Hossain, Michael R. Chernick, Robert F. Padera, Jr., Robert Langer, Daniel G. Anderson, and Janet A. Sawicki.

Cancer Res. 2009 69: 6184-6191.

Published August 1, 2009.

doi: 10.1158/0008-5472.CAN-09-0061

Additional source: American Association for Cancer Research.

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Section Issues On Medicine: Women health