Fast and effective mechanism combats ovarian tumors

A new type of strategy has been proposed to tackle an aggressive subtype of ovarian cancer by using a nanoscale drug-delivery system designed to target specific cancer cells. Scientists have devised a cluster of nanoparticles called gagomers, made of fats and coated with a kind of polysugar. When filled with chemotherapy drugs, these clusters accumulate in tumors, producing dramatic therapeutic benefits.

Ovarian cancer accounts for more deaths among American women than any other cancer of the female reproductive system. According to the American Cancer Society, 1 in 72 American women will develop ovarian cancer, and 1 in 100 will ultimately die of the disease.

This research has two objectives: to provide a specific target for anticancer drugs to increase their therapeutic benefits, and to reduce the toxic side effects of anticancer therapies. The study, led by Dan Peer, PhD, of Tel Aviv University in Israel, was published in ACS Nano (2014; doi:10.1021/nn500205b).

Peer explained that traditional courses of chemotherapy are not an effective line of attack. Chemotherapy's failing lies in the inability of the medicine to be absorbed and maintained within the tumor cell long enough to destroy it. In most cases, the chemotherapy drug is almost immediately ejected by the cancer cell, severely damaging the healthy organs that surround it, leaving the tumor cell intact.

But with their new therapy, Peer and his colleagues saw a 25-fold increase in tumor-accumulated medication and a dramatic dip in toxic accumulation in healthy organs. Tested on laboratory mice, the gagomer mechanism effects a change in drug-resistant tumor cells. Receptors on tumor cells recognize the sugar that encases the gagomer, allowing the binding gagomer to slowly release tiny particles of chemotherapy into the cancerous cell. As more and more drugs accumulate within the tumor cell, the cancer cells begin to die off within 24 to 48 hours.

"Tumors become resistant very quickly. Following the first, second, and third courses of chemotherapy, the tumors start pumping drugs out of the cells as a survival mechanism," said Peer. "Most patients with tumor cells beyond the ovaries relapse and ultimately die due to the development of drug resistance. We wanted to create a safe drug-delivery system, which wouldn't harm the body's immune system or organs."

Peer chose to tackle ovarian cancer in his research because his mother-in-law passed away at age 54 years from the disease. "She received all the courses of chemotherapy and survived only a year and a half," he said. "She died from the drug-resistant aggressive tumors.”

"At the end of the day, you want to do something natural, simple, and smart. We are committed to try to combine both laboratory and therapeutic arms to create a less toxic, focused drug that combats aggressive drug-resistant cancerous cells," said Peer. "We hope the concept will be harnessed in the next few years in clinical trials on aggressive tumors."

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