Mount Sinai Discovers Factors That Improve Ovarian Cancer Survival
Mount Sinai School of Medicine researchers have made a discovery that results in the elimination of tumor cells associated with ovarian cancer.
Mount Sinai School of Medicine researchers have made a discovery that results in the elimination of tumor cells associated with ovarian cancer. For the first time, the research demonstrated prolonged survival in a mouse model of cancer by injecting a new class of molecules that specifically silence an oncogene, a mutated gene that causes the growth of cancer cells. These findings appear in the journal Cancer Research.
Ovarian cancer is the most lethal of all gynecologic cancers in the United States, with an estimated 15,520 deaths from among 21,650 newly diagnosed cases annually. Ovarian tumors are notorious for recurring and developing resistance to chemotherapy. Women with late-stage tumors have a five-year survival rate of only 30 percent.
The target oncogene for this study, KLF6-SV1, has been shown previously by Mount Sinai researchers to be excessively produced in a number of different cancers, including ovarian, prostate, hepatocellular and lung, and has been correlated with poor patient outcome and survival.
Our results provide the proof-of-principle that therapeutic targeting of this oncogene, KLF6-SV1, can markedly increase survival in a mouse model of ovarian cancer, said senior author John Martignetti, MD, PhD, Associate Professor in the Departments of Genetics and Genomic Sciences, Pediatrics, and Oncological Sciences at Mount Sinai School of Medicine. "Ultimately, we hope to translate these findings into novel treatments for helping women with ovarian cancer live longer."
For the study, lead author Dr. Analisa DiFeo, Dr. Martignetti, and their colleagues, treated ovarian cancer-bearing mice with injections in the abdomen of a novel class of chemically-modified small interfering molecules (siRNA) targeting KLF6-SV1. Treatment resulted in elimination of the tumors and significant increases in survival. Median survival was tripled from 114 days to 311 days, while overall survival was more than doubled surpassing 450 days.
This study also revealed how KLF6-SV1 protects tumor cells from dying. Dr. DiFeo’s work shows that high levels of KLF6-SV1 prevent tumor cells from entering a death pathway known as apoptosis. Therefore, therapeutically targeting KLF6-SV1 for elimination should accelerate tumor cell death and make other chemotherapeutic agents already in use more effective across a broad range of different cancers, said Dr. Martignetti.
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses The Mount Sinai Hospital and Mount Sinai School of Medicine. The Mount Sinai Hospital is one of the nation’s oldest, largest and most-respected voluntary hospitals. Founded in 1852, Mount Sinai today is a 1,171-bed tertiary-care teaching facility that is internationally acclaimed for excellence in clinical care. Last year, nearly 50,000 people were treated at Mount Sinai as inpatients, and there were nearly 450,000 outpatient visits to the Medical Center.
Mount Sinai School of Medicine is internationally recognized as a leader in groundbreaking clinical and basic-science research, as well as having an innovative approach to medical education. With a faculty of more than 3,400 in 38 clinical and basic science departments and centers, Mount Sinai ranks among the top 20 medical schools in receipt of National Institute of Health (NIH) grants.