New Target for Treatment of Ovarian Cancer

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A protein that plays a key role in regulating the onset of cell division has been identified as a potential target for the treatment of ovarian cancer. The research, published by Cell Press in the August issue of the journal Cancer Cell, provides evidence that combination therapies targeting different phases of the cell division cycle are highly desirable for optimal cancer treatment.

Mitosis is one phase of the cell cycle that divides a single cell into two new but genetically identical daughter cells. It is a complex and highly regulated sequence of events that occurs in a series of well-defined stages.

It is well established that uncontrolled mitosis is a defining characteristics of cancer cells. Although chemotherapeutic drugs that inhibit mitosis, such as the taxanes, have been used to successfully treat multiple types of cancer, some are resistant to this type of chemotherapy.

"A significant proportion of ovarian cancers fail to respond to taxanes, leading to the emergence of resistant disease," says senior study author Dr. Robert C. Bast, Jr. from the M.D. Anderson Cancer Center. "There is a pressing need for the discovery of synergistic therapies that may improve ovarian cancer response to taxane-based chemotherapy and overall prognosis."

Dr. Bast, co-author Dr. Ahmed Ashour Ahmed, and their colleagues were interested in identifying new therapeutic targets that enhance the ability of taxanes to inhibit mitosis while at the same time provide mitosis-independent mechanisms of cancer cell death.

"We discovered that a high level of Salt Inducible Kinase 2 (SIK2) gene was associated with lower chances of survival in ovarian cancer patients. 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," explains Dr. Ahmed.

"Taken together, our results reveal a previously unrecognized role of SIK2 in regulating cell cycle progression and identify SIK2 as an attractive target for treatment of ovarian cancer," concludes Dr. Bast.

The researchers include Ahmed Ashour Ahmed, M.D. Anderson Cancer Center, University of Texas, Houston, TX, University of Cambridge, Cambridge, UK; Zhen Lu, M.D. Anderson Cancer Center, University of Texas, Houston, TX; Nicholas B. Jennings, M.D. Anderson Cancer Center, University of Texas, Houston, TX; Dariush Etemadmoghadam, Peter MacCallum Cancer Center, East Melbourne, Victoria, Australia; Luisa Capalbo, University of Cambridge, Cambridge, UK; Rodrigo O. Jacamo, M.D. Anderson Cancer Center, University of Texas, Houston, TX; Nuno Barbosa-Morais, University of Cambridge, Cancer Research UK Cambridge Research Institute, Cambridge, UK; Xiao-Feng Le, M.D. Anderson Cancer Center, University of Texas, Houston, TX; Australian Ovarian Cancer Study Group, Pablo Vivas-Mejia, M.D. Anderson Cancer Center, University of Texas, Houston, TX; Gabriel Lopez-Berestein, M.D. Anderson Cancer Center, University of Texas, Houston, TX; Geoffrey Grandjean, M.D. Anderson Cancer Center, University of Texas, Houston, TX; Geoffrey Bartholomeusz, M.D. Anderson Cancer Center, University of Texas, Houston, TX; Warren Liao, M.D. Anderson Cancer Center, University of Texas, Houston, TX; Michael Andreeff, M.D. Anderson Cancer Center, University of Texas, Houston, TX; David Bowtell, Peter MacCallum Cancer Center, East Melbourne, Victoria, Australia; David M. Glover, University of Cambridge, Cambridge, UK; Anil K. Sood, M.D. Anderson Cancer Center, University of Texas, Houston, TX; and Robert C. Bast, Jr., M.D. Anderson Cancer Center, University of Texas, Houston, TX.

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