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Frontiers in the fight against ovarian cancer

Women battling ovarian cancer, one of the toughest malignancies known, heard some encouraging news recently from a Stanford researcher on the forefront of new treatments.

Clinical trials are getting underway to test whether the body’s immune system can be “taught” to recognize and kill ovarian cancer cells, explained Oliver Dorigo, MD, PhD, at a lecture sponsored by the Stanford Women’s Cancer Center and the Stanford Health Library. One advantage of this approach is that it targets cancer cells and leaves healthy cells alone. If this strategy proves effective, one day the treatment could be given to patients within a week of their initial surgery to remove the cancer and boost their chances of survival.

Women with this illness face a rough road. Ovarian cancer is the 10th most common cancer in the United States, but the fifth most common death from cancer. While the chance of surviving at least five years is better than 90 percent when the disease is caught early, most of the time that doesn’t happen. That’s because the early symptoms of ovarian cancer are so vague – including bloating and pain in the abdomen – that few women realize it’s serious and see a doctor, said Dorigo, who is an associate professor and director of the Division of Gynecologic Oncology at Stanford Women’s Cancer Center.

Instead, most ovarian cancer is diagnosed at a late stage after it has spread, and the five-year survival rate is only about 30 percent. Although researchers have poured time and resources in a huge effort to produce better treatments, progress has been only incremental in the past decade, Dorigo explained.

Once ovarian cancer is diagnosed, the standard treatment is surgery to remove as much of the tumor disease as possible, followed by chemotherapy. Patients whose cancer can be completely removed in surgery have a better prognosis compared to patient in which this is not possible.

The past decade has brought advances in treatment. Surgeons now use small-incision, or laparoscopic, tools to remove cancer. Chemotherapy includes a combination of drugs that together mount a stronger defense against cancer recurring. In some patients, the drugs can be delivered directly into the abdomen, rather than by intravenous line, which might make a big difference in the overall prognosis, Dorigo said.

Still, the huge effort to find a chemotherapy that knocks out ovarian cancer’s return has yielded only incremental progress, according to Dorigo. So researchers are pursuing more treatment strategies.

A group of drugs called PARP inhibitors attacks cancer in a novel way, by blocking a cancer cell’s ability to repair damage to its DNA. One study found at least 50 percent of cancer patients getting a PARP inhibitor, called olaparib, had their tumors shrink. Dorigo pointed out that these drugs are mainly effective in patients with BRCA gene mutations. Despite that response, later studies found that overall survival didn’t improve in the ovarian cancer patients getting this drug, Dorigo said.

One of the most promising strategies ahead is a treatment that would activate the body’s own immune system against cancer. Doctors have long been mystified that the immune system’s natural defenses don’t seem to work against cancer. Recent research has found a possible explanation: Tumors contain a substance that works like a “stop sign” to block immune cells from attacking. That stop sign, called an immune inhibitory molecule, has now become the target of new studies.

Researchers are racing to find a treatment that knocks down this stop sign and enables the immune system to attack the cancer. The race is on to start trials of this treatment strategy in ovarian cancer patients. Stanford plans to start such a trial next year, Dorigo said.

While every ovarian cancer patient is different, there are ways for each to benefit from advances in treatment and care. For more information, patients and their families can consult the Stanford Cancer Institute’s website. The site, Dorigo said, has a search engine that can be used to find which of the 12 currently open clinical trials are relevant to individual patients. Information is also available from the Stanford Cancer Clinical Trials Office at 650-498-7061 or ccto-office@stanford.edu.

Although Dorigo has high hopes for trials getting underway on immune therapy, he’s also aware that expectations don’t always last. “For us, the goal is always a cure,” Dorigo said. “But sometimes, we have to be more realistic.”

Donna Alvarado is a Bay Area-based writer and editor who volunteers at the Stanford Health Library and finds inspiration in medical and health topics.

Previously: Ovarian cancer biomarkers may enable personalized treatment, say Stanford scientists, Stanford expert weighs in on ovarian-cancer screening recommendation and Ovarian cancer tests flawed

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