Two drugs never used together before in treating ovarian cancer killed 70% of cells already resistant to commonly used chemotherapy compounds, concludes a new study published online recently in Gynecologic Oncology. Lead author Dr Prakash Vishnu from the Mayo Clinic in Jacksonville, Florida, and colleagues, hope the combination of ixabepilone and sunitinib will offer women with advanced ovarian cancer a much needed treatment option.
Late stage ovarian cancer is often fatal because it becomes progressively resistant to the chemotherapy compounds currently used to treat it.
Co-author Dr Gerardo Colon-Otero, a hematologist-oncologist who treats patients with ovarian cancer said in a statement issued on Wednesday that:
“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.”
The “proof of principle” study also found that a cellular protein called RhoB, which is activated by the two-drug combination, plays a vital role.
RhoB belongs to a family of proteins that act as “molecular switches” that send important signals in cellular processes such as gene expression, cell proliferation and apoptosis or “cell suicide”.
Study senior author and cancer biologist Dr John Copland had already identified RhoB as a key modulator in helping drugs kill other types of tumor, but this is the first time RhoB has been identified as having a role in ovarian cancer.
“Now we find that with this combination of drugs, RhoB is increased and cells die,” said Copland.
Copland said RhoB is a potential biomarker that may help identify which ovarian cancer patients might benefit from the new chemotherapy drug combination.
The idea for the study arose because Copland and the team at his lab, including co-author Laura Marlow, had set up two new ovarian laboratory cell lines derived from tumor tissue taken from a patient whose ovarian cancer had spread and had stopped responding to chemotherapy treatments.
Colon-Otero suggested that Copland and his team try the two drugs on their new cell lines.
They found that in both cell lines, the proportion of cells killed was much greater when the drugs were used together than when they were used separately.
In the chemotherapy-resistant lines, ixabepilone killed up to 30% of cells, and suntinib up to 10%. But when used together, the kill rate was 70%.
Ixabepilone is a taxane that targets microtubules and thereby stops diving cells from being able to form a spindle, an essential element of cell division. Sunitinib is a tyrosine kinase inhibitor that stops growth signals from reaching inside cancer cells.
Neither drug is currently approved for treatment with ovarian cancer. Ixabepilone is currently approved for use in metastatic breast cancer, and sunitinib for use in kidney cancer.
Written by Catharine Paddock PhD