NFCR Scientists Discover Surprising New Target for Ovarian Cancer

NFCR Scientists Discover Surprising New Target for Ovarian Cancer

National Foundation for Cancer Research Makes New Step Toward Enhancing Anti-Cancer Drugs

The National Foundation for Cancer Research (NFCR) has opened a large window of opportunity to improve the effectiveness of existing chemotherapies against ovarian cancer. For the first time, the protein Salt Inducible Kinase 2 (SIK2) has been found to play a critical role in cell division and regulating the response of ovarian cancer to chemotherapy. This discovery means that scientists have a new pathway to explore to increase the sensitivity of ovarian cancer cells to anti-cancer drugs.

This research was reported in the August issue of Cancer Cell by NFCR scientists, Robert C. Bast, Jr., M.D. and Ahmed Ashour Ahmed, M.D., Ph.D. Dr. Bast and Ahmed are with the University of Texas MD Anderson Cancer Center and the University of Oxford.

Only about half of women with ovarian cancer will respond to a taxane, which is a standard type of chemotherapy agent. This dramatic lack of response resulted in an urgent call to researchers to find a new treatment to fight this cancer.

NFCR researchers, Ahmed and Bast, answered the call by using nearly 780 pools of siRNAs, (strands of genetic material involved in decoding DNA instructions) to knock down different proteins that might alter cell sensitivity to the chemotherapy agent. One of the most promising proteins, the enzyme SIK2, was an unlikely candidate, as it is normally associated only with cell metabolism. However, Dr. Ahmed and Bast discovered that SIK2 also plays a key role in the beginning stages of cell division.

Dr. Ahmed and Bast demonstrated that depleting SIK2 from ovarian cancer cells in laboratory models also sensitized the cells to taxanes, which are known to inhibit cell division. This may lead to enhancement of taxane-based drugs to make them more effective in inhibiting or even stopping the cancer's growth in a larger fraction of patients. These findings demonstrate once again that combination therapies targeting different phases of the cell division cycle are vital for new and better approaches to treating cancer.

"The discovery that SIK2 plays a role in cell cycle regulation is groundbreaking, since, to date, it has only been linked to cellular metabolism and energy balance," Dr. Ahmed said. "In addition to improving the response of some cancers to a taxane, our findings add support to emerging evidence that cancer cell metabolism and cell division functions are coupled."

Dr. Bast, Vice President for Translational Research at MD Anderson, credits this discovery to NFCR's long-standing support of their research. For ten years, NFCR has supported Dr. Bast in his search for more effective ways to treat ovarian cancer. "NFCR understands that it is only through this type of long-term support of research that we will unlock the intricate and complex mysteries of cancer to benefit patients with this disease," said Bast.

Finding drugs that inhibit SIK2 could improve cancer treatment significantly. Such drugs do not yet exist, but, thanks to NFCR scientists, the critical first step of identifying a promising target has been achieved.

"This research breakthrough will set in motion the drug discovery process to identify inhibitors of SIK2," said Dr. Michael Wang, NFCR Chief Science Officer. "Ovarian cancer patients are in great need of new approaches that allow us to be more effective than anything we now have available. This new understanding of how treatment may be enhanced looks very promising."

About the National Foundation for Cancer Research

The National Foundation for Cancer Research (NFCR) is a leading cancer research charity dedicated to funding cancer research and public education relating to cancer prevention, earlier diagnosis, better treatments and, ultimately, a cure for cancer. NFCR promotes and facilitates collaboration among scientists to accelerate the pace of discovery from bench to bedside.

Since 1973, NFCR has provided over $288 million in support of discovery-oriented cancer research focused on understanding how and why cells become cancerous, and on public education relating to cancer prevention, detection, and treatment. NFCR scientists are discovering cancer's molecular mysteries and translating these discoveries into therapies that hold the hope for curing cancer. NFCR is about Research for a Cure-cures for all types of cancer. For more information, please visit www.NFCR.org.

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