Mayo Clinic researchers find drug duo kills chemotherapy-resistant ovarian cancer cells

The use of two drugs never tried in combination before in ovarian cancer resulted in a 70 percent destruction of cancer cells already resistant to commonly used chemotherapy agents, say researchers at Mayo Clinic in Florida. Their report, published online in Gynecologic Oncology, suggests that this combination (ixabepilone and sunitinib), might offer a much needed treatment option for women with advanced ovarian cancer. When caught at late stages, ovarian cancer is often fatal because it progressively stops responding to the chemotherapy drugs used to treat it.

"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," says study co-author Gerardo Colon-Otero, M.D., a hematologist-oncologist who cares for ovarian cancer patients.

The finding also highlights the importance of the role of a molecule, RhoB, that the researchers say is activated by the drug duo. The study's senior investigator, cancer biologist John Copland, Ph.D., has identified RhoB as a key modulator for drug response in other tumor types, but says its role in ovarian cancer was unknown before this study.

"Now we find that with this combination of drugs, RhoB is increased and cells die," he says.

The study was possible because Dr. Copland and his laboratory colleagues, including co-author Laura Marlow, created and characterized two new ovarian laboratory cell lines. They were derived from tumor tissue specimens taken from a patient with metastatic cancer whose tumors had stopped responding to multiple chemotherapy drugs.

Dr. Colon-Otero suggested trying the two drugs on the new cells lines. Neither drug is approved for use in ovarian cancer. Ixabepilone is a chemotherapy drug that, like other taxane drugs, targets the microtubules and stops dividing cells from forming a spindle. It has been approved for use in metastatic breast cancer. Sunitinib, approved for use in kidney cancer, belongs to a class of tyrosine kinase inhibitors that stops growth signals from reaching inside cancer cells.

Prakash Vishnu, M.D., a former fellow at Mayo Clinic in Florida who is now at the Floyd and Delores Jones Cancer Institute in Virginia Mason Medical Center, Seattle, is the first author of the article and led the study under the mentorship of Drs. Colon-Otero and Copland. He found that in both cell lines, cell kill was significantly greater with the combination than use of either drug alone. For example, in chemotherapy-resistant lines (where this potential combination therapy will most likely be used), ixabepilone alone killed up to 30 percent of cells, and the rate for suntinib was up to 10 percent. When the agents were used together, the kill rate was 70 percent.

Dr. Copland said that RhoB is a potential biomarker that may help identify patients who might benefit from such combination therapy.

The study was funded by Mayo Clinic. Additional co-authors included Joseph Santoso, M.D., of the University of Tennessee and Kevin Wu, M.D., of Mayo Clinic, as well as undergraduate students Gregory Kennedy and William Kennedy from Dr. Copland's laboratory. The researchers declare no conflicts of interest.

About Mayo Clinic
Mayo Clinic is a nonprofit worldwide leader in medical care, research and education for people from all walks of life.

Most Popular Now

AstraZeneca takes next steps towards broad and equ…

AstraZeneca has taken the next steps in its commitment to broad and equitable global access to the University of Oxford’s COVID-19 vaccine, following landmark agreements ...

Johnson & Johnson announces acceleration of it…

Johnson & Johnson (NYSE: JNJ) (the Company) today announced that through its Janssen Pharmaceutical Companies (Janssen) it has accelerated the initiation of the Phase 1/2...

Low-cost dexamethasone reduces death by up to one …

In March 2020, the RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial was established as a randomised clinical trial to test a range of potential treatments for C...

Sanofi invests to make France its world class cent…

Sanofi detailed plans on how the Company will make significant investments in France to increase its vaccines research and production capacities, and contribute in respon...

Calquence showed promising clinical improvement in…

Results published in Science Immunology showed that Calquence (acalabrutinib), a Bruton’s tyrosine kinase (BTK) inhibitor, reduced markers of inflammation and improved cl...

Super-potent human antibodies protect against COVI…

A team led by Scripps Research has discovered antibodies in the blood of recovered COVID-19 patients that provide powerful protection against SARS-CoV-2, the coronavirus ...

New consortium EUbOPEN will provide tools to unloc…

Almost twenty years after deciphering the human genome, our understanding of human disease is still far from complete. One of the most powerful and versatile tools to bet...

AstraZeneca to supply Europe with up to 400 millio…

AstraZeneca has reached an agreement with Europe's Inclusive Vaccines Alliance (IVA), spearheaded by Germany, France, Italy and the Netherlands, to supply up to 400 milli...

Up to 45 percent of SARS-CoV-2 infections may be a…

An extraordinary percentage of people infected by the virus behind the ongoing deadly COVID-19 pandemic never show symptoms of the disease, according to the results of a ...

Researchers identify potent antibody cocktail to t…

Researchers at the University of Maryland School of Medicine (UMSOM) evaluated several human antibodies to determine the most potent combination to be mixed in a cocktail...

Gilead announces results from Phase 3 Trial of rem…

Gilead Sciences, Inc. (Nasdaq: GILD) announced topline results from the Phase 3 SIMPLE trial in hospitalized patients with moderate COVID-19 pneumonia. This open-label st...

Mayo finds convalescent plasma safe for diverse pa…

Mayo Clinic researchers and collaborators have found investigational convalescent plasma to be safe following transfusion in a diverse group of 20,000 patients. The findi...