The goals of the Ovarian Cancer Institute are to find an early diagnostic tool for this disease, to understand the molecular basis of ovarian cancer and to better understand the causes of chemotherapy resistance, leading to the ultimate goal of developing more effective therapies in the treatment of the disease.

Called the silent killer, ovarian cancer is the leading cause of death from gynecologic cancers in the United States. It will strike 1 in 57 women in America this year. Because there are no obvious symptoms, the cancer is often detected too late.

OCI is dedicated to changing the odds for women who may face no better than an average 5-year survival rate. And this statistic has not changed in 30 years.

Visit the McDonald Laboratory website for the most up-to-date information on research efforts.


THE RESEARCHERS

John McDonald, PhD, OCI Chief Scientific Officer, Associate Dean and Director of the Integrated Cancer Research Center, Georgia Institute of Technology

Formerly Head of the Department of Genetics Department at the University of Georgia, Dr. John McDonald, now holds the position of Associate Dean and Director of the Integrated Cancer Research Center at Georgia Tech. Dr. McDonald, is a recognized world authority in molecular genetics and genomics. Dr. McDonald's combined skills in both molecular and computational genetics, uniquely qualify him to direct OCI's high-throughput genetic analysis approach to various stages and types of ovarian tumors.

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RESEARCH UPDATE

Personalized Cancer Therapy Project
The traditional approach to cancer chemotherapy is to find a drug that effectively arrests cancer cells grown in laboratory culture conditions. Promising drugs are next tested in animal models. If the drug passes these tests, it moves to Phase I experimental trials in humans. The effectiveness of an experimental drug in humans is determined by monitoring how well it does in reducing tumor growth in the majority of patients tested. Many drugs that work dramatically well in a few patients but not in the majority of patients are discarded and not granted FDA approval for general use. We now realize that this approach is flawed because cancer is not one single disease. There is extensive genetic variation among even the same family of cancers (e.g., ovarian cancers) and between specific cancer patients. This means that not only may cancers progress differently in different cancer patients but those patients may respond differently to the same anti-cancer drug. The promise of a personalized approach to drug therapy is based on our current ability to genetically characterize each patient’s tumor on the molecular level. By analyzing each patient’s tumor individually, we hope to be able to predict the particular drug or drug combination that would be optimal for the treatment of each individual patient. OCI researchers are currently analyzing individual ovarian cancers and developing algorithms whereby they can predict the optimal therapeutic drug for each patient.

Early Diagnostic Test for Ovarian Cancer Project
Ovarian cancer is often called the “silent killer” because it is essentially asymptomatic until the cancer has progressed to advanced stages. There is a dire need for an accurate diagnostic test for ovarian cancer. In collaboration with GA Tech’s Chemistry professor, Dr. Facundo Fernandez, OCI researchers are working on a mass spectrometric based assay for ovarian cancer. Unlike previous efforts that have focused on monitoring changes in blood protein levels the OCI test monitors changes in metabolic levels. Metabolites are much smaller and less abundant molecules than proteins and as a result can be more easily and reliably monitored than proteins. The test requires only a single drop of blood and requires only minutes to perform.
Over the past year we have demonstrated that our test is 100% accurate over 100 patient samples thus far examined. This is the most accurate diagnostic test for ovarian cancer thus far reported. We are currently expanding the number of samples examined in order to demonstrate the robustness of the test prior to applying for FDA approval for clinical use.

Ovarian Cancer Stem Cell Project
Cancer stem cells (a.k.a., cancer initiating cells) are the origin of cancers. These stem cells are typically embedded within tumors in low frequency (it has been estimated that less than 1% of the cancer cells making up a tumor are cancer stem cells). Unlike the bulk of cancer cells making up a tumor, cancer stem cells do not replicate rapidly. Most cancer drugs (e.g., standard ovarian cancer drugs cis-/carboplatin and taxol) have been selected for use because they attack rapidly dividing cells. These drugs often do attack and kill the majority of cancer cells making up a tumor, but they may not kill cancer stem cells. This may explain why ovarian and other types of tumors often reoccur. OCI researchers have been able to isolate ovarian cancer stem cells from both ovarian cancer cell lines and from ovarian cancer cells present in ascites fluid. Over the past year, these researchers have shown that ovarian cancer stem cells are NOT effectively killed by the drugs commonly used in the treatment of ovarian cancer. We are currently developing new therapies that can either directly kill ovarian cancer stem cells or stimulate these stem cells to be converted to the type of cancer cells that can be killed by conventional therapies.

Novel Drug Development Project
In collaboration with the laboratory of Georgia Tech Scientist Dr. Jeff Skolnick, OCI researchers have pioneered efforts to demonstrate the anti-cancer properties of metabolites. Metabolites are the naturally occurring products of enzyme reactions that occur in all living beings including humans. Dr. Skolnick’s group takes information on gene expression patterns in ovarian cancer cells and uses state-of-the-art computer algorithms to predict metabolic changes that have occurred in these cells. These predictions are then experimentally tested in the OCI laboratory. Preliminary studies conducted over the past year have demonstrated that some metabolites are more effective at arresting cancer cell growth than many drugs in current clinical practice. These studies have received considerable attention in the scientific and popular press (See, for example: cssb.biology.gatech.edu/news). Additional areas of investigation involve the development of compounds derived from plants that have shown promise in killing cancer stem cells.


The Use of Nanoparticles in the Treatment of Ovarian Cancer

Magnetic Nanoparticle Project
Most ovarian cancer metastases are caused by cancer cells sloughing off the primary tumor into the abdominal cavity and spreading to the omentum, liver and other abdominal organs. In collaboration with Dr. John Zhang in the School of Chemistry, OCI scientists have constructed magnetic nanoparticles that can be specifically targeted to ovarian cancer cells. We have recently shown that these nanoparticles can be used to attach to free floating ovarian cancer cells within the abdomen (ascites fluid) of ovarian cancer patients and subsequently harvested by subjecting the nanoparticles to a magnetic field. These findings have been extensively discussed in the scientific and popular press (See, for example: www.technologyreview.com/biomedicine/21112/ ). We are currently working on the development of a perfusion system whereby ovarian cancer cells within the abdominal cavity can be exposed to the nanoparticles and captured in a magnetic trap outside the body.

Targeted Drug Delivery With Nanohydrogels
Chemotherapy treatment is hindered because the levels of drugs necessary to kill cancer cells cannot be tolerated by many patients. One possible solution to this problem is to develop methods whereby drugs can be selectively delivered to cancer cells without affecting healthy non-cancer cells. In collaboration with Dr. Andrew Lyon in the School of Chemistry at Georgia Tech, OCI scientists have developed nanohydrogel spheres that can be filled with chemotherapeutic agents and specifically targeted to ovarian cancer cells. We have recently published a series of papers demonstrating the utility of this method of targeted drug delivery to attach ovarian cancer cells in culture. We are currently demonstrating the utility of the method in mouse model systems.