Cancer-killing virus and doxorubicin act synergistically on metastatic ovarian cancer

Cancer-killing virus and doxorubicin act synergistically on metastatic ovarian cancer
Cancer-killing virus and doxorubicin act synergistically on metastatic ovarian cancer

Ovarian cancer is metastatic at the time of diagnosis in more than 75% of women, and the 5-year survival rate is dismal. But a new approach to treatment using a cancer-killing virus combined with a chemotherapy drug may offer hope to those with advanced and recurrent forms of the disease.

The genetically engineered virus 34.5ENVE is oncolytic and has significant antitumor activity against ovarian cancer on its own. This activity is even greater when the virus is combined with doxorubicin to treat disseminated peritoneal ovarian cancer in a mouse model. Doxorubicin was chosen for this study because it is used to treat recurrent ovarian cancer in women.

"Our findings suggest that this could be a promising therapy, and we believe it should be developed for the treatment of recurrent or refractory ovarian cancer in humans," said Balveen Kaur, PhD, professor of neurological surgery at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

More than 70% of women with metastatic ovarian cancer at the time of diagnosis experience tumor recurrence after treatment. The recurrent tumors may develop from cancer cells that are resistant to chemotherapy and are able to survive treatment. The new treatment may be effective because it targets those cells.

The oncolytic herpes simplex virus 34.5ENVE targets cancer cells that overexpress the protein nestin, and inhibits the growth of blood vessels to tumors.

Kaur and her colleagues assessed the anticancer activity of the oncolytic virus 34.5ENVE using several ovarian cancer cell lines, human and mouse tumor cells, and a mouse model of disseminated peritoneal ovarian cancer. Key findings included

  • The expression of nestin was 10 to 100 times greater in human ovarian tumor cells compared with normal ovarian cells;
  • In a mouse model of disseminated peritoneal ovarian cancer, the combination of doxorubicin and the oncolytic virus increased survival, with an average survival of 58 days for treated animals versus 32.5 days for controls;
  • The combination of doxorubicin and the oncolytic virus showed a synergistic increase in apoptosis (programmed cell death) in ovarian cancer cells compared to each agent alone.

"This study underscores the importance of combining the oncolytic virus with doxorubicin for patients who have developed resistance to primary chemotherapy," Kaur said.

This study was published in Clinical Cancer Research (doi: 10.1158/1078-0432.CCR-14-0463).

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