NCI renews SPORE grant for the diagnosis and treatment of ovarian cancer

First awarded in 1999, the grant will provide for more than $13 million in team science efforts between the 2 institutions

National Cancer Institute (NCI) has renewed a $11.5 million Specialized Program of Research Excellence (SPORE) grant in prevention, diagnosis and treatment of ovarian cancer, which supports multidisciplinary research at Fox Chase Cancer Center and the University of Pennsylvania. First approved in 1999, this marks the third five-year term for the Fox Chase-Penn Ovarian SPORE.

"The SPORE program has always been a bold experiment in team science, and we are proud to see the progress of the Fox Chase-Penn SPORE recognized through this grant renewal," says Michael Seiden, M.D., Ph.D., president and CEO of Fox Chase Cancer Center and principal investigator of the Ovarian Cancer SPORE. George Coukos, M.D., from Penn and Andrew K Godwin, Ph.D., of Fox Chase, serve as co-principal investigators on this SPORE.

According to Seiden and his colleagues, the Fox Chase-Penn SPORE has generated many positive ripple effects across both NCI-designated Cancer Centers. Since the inception of the program, both Penn and Fox Chase have invested an additional $13.4 million in support of gynecological oncology clinical and research infrastructure. The SPORE has also served as an important career development for young investigators and an incubator for new lines of scientific inquiry. In the last five years, alone, Fox Chase-Penn SPORE research has generated over $10 million in related grants.

"We have been able to leverage the expertise gained through SPORE research to recruit and foster the talents of many young investigators over the last decade," Seiden says. "This in turn has led to the adoption of new techniques and technologies that have advanced the science of ovarian cancer and will - we have every reason to anticipate - advance clinical care, as well."

The Fox Chase-Penn SPORE focuses on three central concepts in ovarian cancer. The first is epigenetics, the study of modifications made to the human genome that influence how genes are "read" and how they might influence cancer progression. The second is the discovery and validation of predictive biomarkers, chemical signals within the body that provide evidence on the biology of a particular type of cancer and may offer clues for patient prognosis and response to certain therapies. The third is the development of targeted therapeutics, drugs that are specific for particular molecular structures exhibited on the surface of cancer cells.

The SPORE grant primarily funds five main research projects, outlined below, as well as three "core" facilities, which support the research efforts. The core facilities consist of an Administrative Core to oversee research efforts; a Biosample and Tissue Procurement Core to collect and categorize tissue samples for study; and a Biostatistics and Data Management Core to support the researchers ability to analyze the data they collect. The five research projects include:

1. Gene Methylation Signatures for Predictive Classification of Response to Therapy, Co-lead by Fox Chase researchers Paul Cairns, Ph.D., and Mark Morgan, M.D.

Gene methylation (an epigenetic alteration of the genome) of genes related to BRCA1 and BRCA2, may predict how well ovarian cancers respond to particular targeted therapies. Using epigenetic data the SPORE has collected, as well as biosamples from the SPORE repository and national tumor banks, the researchers will test to see how reliably gene methylation predicts sensitivity or resistance to standard and emerging therapies. This could lead to a useful blood test at diagnosis, or at the time of recurrence, of ovarian cancer that could predict the most beneficial therapy and, potentially, a clinical trial of certain targeted therapies that might be able to circumvent the drug resistance.

2. Improving Estimation and Communication of Ovarian Cancer Risk Among BRCA1/2 Carriers to Optimize Decision Making, co-lead by Mary Daly, M.D., Ph.D., Fox Chase, and Timothy Rebbeck, M.D., Penn.

While well known for their involvement in breast cancer, mutations in the BRCA1 and BRCA2 genes - whether inherited or acquired -- also contribute to ovarian cancer. The risk of these mutations, and how to counsel BRCA1/2 mutation carriers, is less well understood. The team lead by Daly and Rebbeck seeks to identify extent of risk factors related to BRCA1/2-associated ovarian cancers and to develop a methodology by which to counsel carriers of the mutation on treatment options including prophylactic removal of the ovaries.

3. Therapeutic Micro RNA Strategies for Ovarian Cancer, co-lead by Lin Zhang, M.D., and Peter. O'Dwyer, M.D. from Penn, and Thomas Hamilton, Ph.D., of Fox Chase

Malignant epithelial ovarian cancer is one of the most common and lethal forms of ovarian cancer. While new therapies have led to increased survival, these patients typically relapse within a few years with a more resistant form of the disease. Recently, the Penn SPORE investigators have found evidence that microRNAs - tiny segments of RNA - have a role in ovarian cancer and could serve as a biomarker for early diagnosis. These microRNAs, which usually help regulate how genes are read, or expressed, are often themselves deregulated in ovarian cancer. Therefore, the researchers believe that microRNAs might be able to help restore the regulation of genes in ovarian cancer and might serve as a therapeutic or enhance the effect of chemotherapy.

4. Targeting Signaling Networks Via Novel RNAi Approaches to Improve Therapy for Ovarian Cancer, co-lead by Fox Chase researchers Andrew Godwin, Ph.D., Erica Golemis, Ph.D., and Russell Schilder, M.D.

While a single genetic mutation might initiate cancer, most tumors have evolved multiple mutations by the time the cancer is diagnosed. This team of researchers plans to use so-called silencing RNA (siRNA) technology to piece together the effects of silencing individual cancer genes along the EGFR signaling pathway in epithelial ovarian cancer. The overall objective is to identify how sets of genes that interact could be attacked through siRNA strands, drugs or combinations thereof, which could then be brought to Phase 1 trials in the clinic.

5. Advancing T Cell Therapy for Ovarian Cancer, co-lead by Penn researchers George Coukos, M.D., Ph.D., Carl June, M.D. and Daniel Powell, Ph.D.

The human immune system is still the most powerful means of attacking disease, however, it has proven difficult to harness this power to fight cancer cells. Over the past five years of SPORE funding, the team lead by Coukos and June have made great progress in understanding the mechanisms by which tumors evade the immune system - and how to disable these mechanisms. The researchers will conduct a Phase I/II clinical trial that will modify a patient's own T cells and then use those T cells in combination with chemotherapy to further stimulate the immune system to attack its own cells.