Advanced-stage ovarian cancer treated with targeted nanomedicine

Date: Dec-10-2013Researchers at Rutgers, the State University of New Jersey, have used a

targeted nanomedicine approach to deliver small molecule drugs and successfully treat mice with

deadly advanced-stage ovarian cancer.

Writing about their work in a recent print issue of the journal Clinical Cancer

Research, the team explains how an out-of-control protein called CD44 aids tumor growth and

development of drug resistance in advanced-stage ovarian cancer.

Ovarian cancer is the deadliest gynecological cancer in the United States. The National Cancer

Institute estimates there will be 22,240 new cases and 14,030 deaths due to the disease in

2013.

It is not easy to spot ovarian cancer in the early stages, and there is no effective screening

method, so most women do not find out they have it until after it has spread to other organs. By

this stage, surgery and chemotherapy are not as effective.

Targeting CD44 to circumvent drug resistance

The 5-year survival rate for patients with advanced-stage ovarian cancer is 30%. The

researchers believe this is mainly because of the activity of the aberrant CD44 protein and its

ability to make the late stage of the disease resistant to drugs.

Study author Dr. Lorna Rodriguez, a gynecologic oncologist and director of the precision

medicine initiative at Rutgers Cancer Institute of New Jersey, explains:

"Once the ovarian cancer becomes drug resistant we cannot cure it. Circumventing the development

of drug resistance is a reasonable approach and very much needed."

In their study paper, the researchers describe how they used small molecules, called inhibiting

RNA molecules, to attack the genes of the excess CD44 protein in metastatic ovarian cancer cells

isolated from patients.

Nanoscale-based drug delivery system (DDS)

The inhibiting RNA molecules were delivered by a nanoscale-based drug delivery system (DDS) that

also included the anticancer drug paclitaxel in the "payload."

They tested the system in mice developed to have a form of ovarian cancer resembling that

found in humans by injecting them with tumor tissue from patients.

The results showed that the treatment killed cancerous cells in the mice, shrank their tumors,

left healthy tissue intact and also caused fewer side effects than conventional drug therapy.

CD44 is not confined to ovarian cancer. It also features in many other cancers, where it is

expressed on the surface of cancer stem cells. Because of this, the researchers believe their

nanomedicine drug delivery may also help treat other cancers.

The next step is to develop a nanomedicine prototype for human consumption and test it in

clinical trials, say the researchers, who hope they have opened a way to new cancer drug treatments

that will significantly improve the prognosis for patients.

In an earlier issue of the same journal, researchers in the UK write about another approach,

based on PARP inhibitor drugs, whereby targeted treatment plus chemotherapy

may benefit ovarian cancer patients with BRCA gene mutations.

Written by Catharine Paddock PhD

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