Biotechnology cancer

New Clinical Trial Combines Two Methods to Defeat Ovarian Cancer

New clinical trial offers combination therapy to directly kill cancer cells and teach the immune system to keep them from coming back.

Fewer than half of women diagnosed with ovarian cancer live for five years or more. Sarah Adams, MD, hopes her new clinical trial will change this outcome. Adams recently opened a clinical trial at The University of New Mexico Comprehensive Cancer Center to test a new approach to defeat ovarian cancer. The clinical trial treats women whose ovarian cancer results from mutated BRCA genes. It uses one drug that kills the ovarian cancer cells and another that boosts the immune system in response to the dying cancer cells.

Ovarian cancer has unclear symptoms and no screening tests that catch it in its early stages. Often, ovarian cancer spreads to other organs before a woman even knows she has it. Surgery and chemotherapy can help women at the beginning of their treatment, and this gave Adams the idea for her new approach.

As a gynecologic oncologist, Adams performs surgery and prescribes chemotherapy for women with cancers of the female reproductive organs. Adams also conducts research. Her research suggested that women with BRCA-related ovarian cancer responded better to some chemotherapy drugs. Others’ research showed that other chemotherapy drugs not only kill cancer cells but also make the immune system more sensitive to them. Adams’ new treatment combines these approaches into what she thinks may be a powerful way to win against ovarian cancer.

BRCA is a set of genes we all carry. Each gene contains the instructions to produce a protein. BRCA proteins help DNA to repair itself when both of its strands break and completely split the molecule in two. If the BRCA genes are mutated, or changed, the resulting proteins do not work properly and the cell cannot repair its DNA. It dies unless it can resort to other repair methods.

Cells with mutated BRCA genes resort to using a DNA-repair protein called PARP. Adams’ therapy uses a type of drug called a PARP inhibitor, which keeps the PARP protein from its repair work. “If you knock out BRCA,” says Adams, “the cell can still live. If you knock out PARP, the cell can still live. But if you knock out both, the cell dies.”

The PARP inhibitor does not affect non-cancerous cells because they have working BRCA proteins to repair DNA. “It’s specific to cancer cells so it’s nicely targeted and there’s minimal toxicity,” says Adams. The therapy is also easy to dispense. “It’s a pill that people take orally,” she says.

Adams’ therapy combines the PARP inhibitor with a specific antibody. An antibody is a protein that attaches to a target cell. The antibody in Adams’ therapy helps one type of immune cell, called a T-cell, to find and devour ovarian tumor cells. Untreated ovarian tumors often produce chemical signals that keep T-cells away. But, the PAPR inhibitor combined with the antibody alert the entire immune system to the ovarian cancer cells.

Once the immune system can find the ovarian cancer cells, it can rid the body of them if the PARP inhibitor doesn’t kill them first. And because the immune system can remember how to respond to ovarian cancer cells, it can continue to rid the body of them if the cancer tries to come back. Adams hopes that this effect will give women long-lasting protection.

The clinical trial is currently open to women with BRCA1 or BRCA2 mutations. Either parent can pass these BRCA mutations to their children. People with BRCA mutations have a higher risk of getting breast and ovarian cancers and may have relatives who had these cancers at young ages.

In pre-clinical studies, this combination therapy got rid of tumors and helped mice to live longer. The clinical trial now makes the therapy available to women with BRCA gene mutations whose ovarian cancer has returned. “I’m very excited about the results we’ve seen so far,” says Adams, “and hopeful that this regimen can achieve long-term benefit for women with ovarian cancer.” Adams’s ultimate goal is to expand the therapy to help all women with ovarian cancer.