Ovarian cancer at this later stage is often fatal since it begins to resist the chemotherapy compounds that are currently used for treatment. According to co-author, Dr. Gerardo Colon-Otero, “Women die from ovarian cancer because their tumors become resistant to chemotherapy, so a drug that might be able to reduce that resistance -- which may be what this combination of agents is doing -- would be a boon to treatment of this difficult cancer."
This study also discovered that a cellular protein called RhoB, which is activated by the drug combination, plays a critical role. RhoB is a protein that functions as a “molecular switch” and is capable of signaling cellular processes such as gene expression, cell division, and cell death.
Senior study author, Dr. John Copland had already identified RhoB as a key player in aiding drugs to kill other types of tumors, but this is the first time that RhoB has been found to play a role in ovarian cancer. Copland adds, "Now we find that with this combination of drugs, RhoB is increased and cells die."
During testing on cell lines, the researchers found that the proportion of cells killed was far greater when the drugs were used in conjunction compared to when they were applied separately. In the chemotherapy resistant lines, ixabepilone killed up to 30% of cells, and suntinib up to 10%. However when applied together, they achieved a kill rate of 70%.
Ixabepilone is a taxane drug that targets microtubules and thus blocks dividing cells from being able to form a spindle, a critical function of cell division. Sunitinib is a tyrosine kinase inhibitor that stops growth signals from penetrating to cancer cells. Neither drug is currently approved for ovarian cancer treatment. Currently, Ixabepilone is used for metastatic breast cancer, and sunitinib is used for kidney cancer.