ARRA Investments in Ovarian Cancer
Public Health Burden
Ovarian cancer accounts for about 3 percent of all cancers diagnosed among women in the United States. It is the most deadly cancer of the female reproductive system and the fifth leading cause of cancer-related death among U.S. women. In 2009, more than 21,000 new cases of ovarian cancer will be diagnosed and more than 14,000 American women will die of this disease.
The high mortality of ovarian cancer reflects the fact that it is mostly diagnosed after the disease has spread. In its early stages, ovarian cancer may not cause specific symptoms, and no standard screening test is available for early diagnosis in women without symptoms. Several ARRA-funded projects are seeking to identify biomarkers that could be used to detect early ovarian cancer, including the following:
A study to develop and validate a panel of multiple protein biomarkers in blood serum that distinguishes women with early ovarian cancer from healthy women and women with benign pelvic disease.
A study that will use powerful new analytic technologies and experimental animals bearing implanted human ovarian tumors to systematically identify new ovarian cancer protein biomarkers in blood plasma; the validity of identified biomarkers will then be assessed in women.
Women with ovarian cancer are usually treated with surgery to remove as much of their cancer as possible. Because most patients are diagnosed with widespread disease, they will be further treated with systemic chemotherapy (drugs injected into the bloodstream). In some cases, chemotherapy drugs may also be introduced directly into the abdominal cavity using a small tube (intraperitoneal chemotherapy). Although these treatments can lengthen the survival of women with ovarian cancer, overall 5-year survival for individuals diagnosed with this disease is less than 50%. Therefore, more effective treatments are urgently needed. ARRA-funded research projects are investigating new approaches to ovarian cancer treatment, including the following:
A phase I trial, being conducted under the Accelerating Clinical Trials of Novel Oncologic Pathways (ACTNOW) program and involving women with advanced ovarian or other types of cancer who have inherited mutations in either the BRCA1 or the BRCA2 gene, to evaluate a drug that blocks the activity of proteins called PARP1 and PARP2 that help repair DNA damage; mutations in BRCA1 and BRCA2 also impair DNA repair, and it is hoped that the combined effects of the drug and the mutations will accelerate the accumulation of DNA damage in cancer cells, causing them to die.
A phase I/II study of a PARP1 inhibitor in combination with an agent that prevents the growth of blood vessels to tumors in the treatment of women with recurrent ovarian cancer.
A study to develop a nanoparticle-like carrier that selectively delivers anticancer drugs directly into ovarian cancer cells, bypassing cellular drug resistance mechanisms; such a carrier system would permit less-toxic, more-effective treatment of drug resistant ovarian tumors.
A study to determine whether positron emission tomography (PET) imaging can be used along with biomarkers to evaluate disease aggressiveness and early treatment response in patients with advanced ovarian cancer; this study could ultimately help clinicians select the most appropriate chemotherapy regimens and spare patients the unnecessary toxic effects of ineffective treatments.
Approximately 10 to 15 percent of ovarian cancers are caused by inherited mutations in either the BRCA1 or the BRCA2 gene. Inherited mutations in several other genes also increase the risk of ovarian cancer. However, genes that play a role in the development of sporadic, or non-inherited, forms of the disease remain to be identified. The identification of these genes could lead to improved ways to prevent, diagnose, and treat ovarian cancer. ARRA-funded research in this area includes the following:
The Cancer Genome Atlas (TCGA) project will comprehensively characterize the genomic changes that occur in more than 20 types of cancer. Ovarian cancer was one of the original cancer types selected for study in TCGA.
A study that will examine DNA sequence polymorphisms in more than 150 genes involved in DNA repair to determine whether variants of these genes increase the risk of ovarian cancer; the researchers will study DNA samples from approximately 7000 women with ovarian cancer and 7000 unaffected women.
Biospecimens, such as blood, tissue, saliva, and urine specimens, are invaluable resources for researchers who are trying to understand cancer and other diseases at their most basic level and, therefore, in efforts to find new ways of preventing, diagnosing, and treating disease. ARRA funding is supporting efforts to improve the collection, annotation, storage, management, and distribution of biospecimens for cancer research. For example:
The Gynecologic Oncology Group (GOG) tissue bank, which has received and processed tissue from more than 6,100 patients and provided over 52,000 specimens to approximately 146 investigators over the last decade, will continue to manage specimens from patients enrolled in clinical treatment trials to maintain an accurate and effective bank of tumor and normal tissues and will promote the availability of specimens to researchers.
-- Multianalyte assay for early diagnosis of ovarian cancer -- Lokshin, Anna A (PA)
-- Identification of ovarian cancer plasma biomarkers -- Speicher, David W (PA)
-- A phase I study of chronically-dosed, single-agent ABT-888 in patients with either BRCA 1/2-mutated cancer; platinum-refractory ovarian, fallopian tube, or primary peritoneal cancer; or basal-like breast cancer -- Egorin, Merrill (PA)
-- Phase I/II study of AZD2171 and AZD2281 in combination for treatment of recurrent platinum-sensitive papillary-serous ovarian, fallopian tube or peritoneal cancer or for treatment of recurrent triple-negative breast cancer -- Kufe, Donald (MA)
-- Intelligent polymeric nanogel technology overcoming drug resistance in ovarian cancer -- Janat-Amsbury, Margit M (UT)
-- FDG PET and biomarkers in treatment response in advanced ovarian cancer -- Rajendran, Joseph G (WA)
-- Functional annotation of cancer genomes: TCGA, glioblastoma and ovarian cancer -- Hahn, William C (MA)
-- The molecular epidemiology of ovarian cancer -- Schildkraut, Joellen M (NC)
-- Gynecologic oncology group -- human specimen bank -- Disaia, Philip J (MD)
Page Last Updated on June 30, 2018
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