Researchers have identified the salt inducible kinase 2 (SIK2) gene, which plays a key role in regulating the onset of cell division, as a potential target for the treatment of ovarian cancer.
The findings, by researchers from the University of Texas M.D. Anderson Cancer Center, Houston, add to the growing evidence that combination therapies targeting different phases of the cancer cell division cycle are needed for optimal treatment.
Although mitosis-inhibiting drugs such as the taxanes have been used successfully to treat multiple types of cancer, only about 50% of patients with ovarian cancer respond to taxanes, and it is not possible to identify in advance which patients will benefit. “There is a pressing need for the discovery of synergistic therapies that may improve ovarian cancer response to taxane-based chemotherapy and overall prognosis,” the authors write in the August issue of Cancer Cell.
The team of researchers was interested in identifying new therapeutic targets that enhance the ability of taxanes to inhibit mitosis while at the same time providing mitosis-independent mechanisms of cancer cell death.
"We discovered that a high level of SIK2 gene was associated with lower chances of survival in ovarian cancer patients,” noted coauthor Ahmed Ashour Ahmed, MD, PhD. “Analysis of ovarian cancer cells revealed that SIK2 played an important role in the progression through the early phases of the cell cycle leading to mitosis and, in addition, controlled the initiation of mitosis. Lowering the level of SIK2 in cancer cells using genetic manipulation reduced the rate of cancer cell growth and acted in synergy with the established mitosis inhibitor, paclitaxel,” he explained.
The authors note that no specific inhibitors for SIK2 are currently available and that such drugs are needed to permit future clinical studies. “Knowing the right target,” they say, “is an important first step.”