The latest in gynecological cancer research from the Pacific Northwest

Dr. Denise Galloway standing behind a Fred Hutch podium — Dr. Denise Galloway speaks about how HPV proteins disrupt the repair of DNA damage during the Northwest Gynecological Cancer Symposium held Dec. 4 at Fred Hutch. Photo by Robert Hood / Fred Hutch News Service

When it comes to cancers that primarily afflict women, breast cancer often gets top billing. But there’s a host of malignancies collectively known as gynecological cancers — ovarian, cervical, endometrial, vaginal and vulvar — that are far less common but can sometimes be more deadly to the women they affect.

Ovarian cancer, for example, affects about 22,000 women every year in the U.S. — less than a 10th of the number of new breast cancer cases diagnosed every year — but it kills about 14,000, according to the American Cancer Society. It’s the deadliest of gynecological cancers in large part because it’s typically diagnosed at very late stages.

Monday, cancer researchers from around the Pacific Northwest gathered at Fred Hutchinson Cancer Research Center to discuss their latest efforts to better prevent, detect and treat these tumors at the inaugural Northwest Gynecological Cancer Symposium.

Organized by the Rivkin Center for Ovarian Cancer, the symposium brought together scientists from Fred Hutch, University of Washington, British Columbia Cancer Agency, University of British Columbia and Oregon Health & Science University as well as some local biotech companies.

The topics presented ranged from nationwide epidemiology studies of ovarian cancer risk factors to the mechanisms of how human papillomaviruses spur the formation of genital cancers at the cellular level.

In a field of relatively rare and often difficult-to-treat diseases, many patients are in need of new therapy options for their cancers. Much of the treatment-focused research presented is still in laboratory development, but the presentations offered a glimpse into what clinical trials may be coming down the pike in the next few years.

For ovarian cancer, diet may matter

Fred Hutch public health researcher Dr. Garnet Anderson presented an overview of findings on ovarian and endometrial cancers from the Women’s Health Initiative, or WHI, which is one of the largest prevention studies addressing postmenopausal women’s health in the U.S. and whose coordinating hub is housed at the Hutch. Anderson is now the head of the WHI Clinical Coordinating Center, which has been running since the early 1990s with funding from the National Institutes of Health.

portrait of Dr. Garnet Anderson — Fred Hutch public health researcher Dr. Garnet Anderson. Photo by Robert Hood / Fred Hutch News Service

The WHI’s most well-known findings relate to breast cancer — namely, that use of combination hormone replacement therapy is linked to an increased risk of that cancer, as well as of cardiovascular disease and stroke. But the research program also included other studies, and other diseases, including gynecological cancers.

As Anderson put it, “gynecological cancers are a relatively rare event, and that’s a good thing.” But that means gathering the data can be a challenge for researchers interested in studying risk factors and ways to prevent these cancers. Anderson’s talk was partly to remind other researchers of the rich resource available in the WHI for others to use — the study enrolled more than 161,000 postmenopausal women around the U.S., more than 115,000 of whom have continued to provide health information for researchers to use.

The WHI also included a diet intervention trial, testing whether a long-term, low-fat diet would reduce the risk of breast cancer. That study failed to show a beneficial effect for overall risk of breast cancer, but Anderson pointed out that a low-fat diet did reduce the risk of ovarian cancer by 17 percent — not a huge shift, but the largest effect they saw in that trial. For women who were eating a high-fat diet before they started on the dietary trial, their reduction in risk of ovarian cancer was even larger.

“And it does look like the longer you’re on a low-fat diet, the more protective it is,” Anderson said.

Ovarian cancer treatment, from precision medicine to immunotherapy

Research presented Monday on new or improved treatments for gynecological cancers focused mainly on ovarian cancer. Talks centered around either precision oncology — or tailoring a treatment for a patient’s own unique tumor — and immunotherapy, an emerging field that harnesses the power of the immune system to fight tumors.

Some of the projects presented included:

Fred Hutch immunotherapy researchers Drs. Kristin Anderson and Christopher Morse, who both work in the laboratory of Dr. Phil Greenberg, presented their laboratory studies using a mouse model to develop an ovarian cancer T-cell therapy. While they’ve identified several roadblocks that stand in the way of a working T-cell therapy for clinical use, the engineered T cells show preliminary promise in killing mouse and human ovarian cancer cells in the lab and extending the animals’ survival.
UW immunotherapy researcher Dr. Denise Cecil presented her work developing a cancer vaccine against ovarian cancer. She and her colleagues in UW’s Cancer Vaccine Institute have seen promising results in a mouse model using a combination of the vaccine and the chemotherapy drug cisplatin to prevent ovarian cancer relapse. They are preparing to soon start an early phase clinical trial of the combination approach.
Dr. Brad Nelson of the BCCA presented recent work exploring how T cells act in a “special ops” way to target specific sets of cells within high-grade serous ovarian tumors, which are the most common type of ovarian cancer. Nelson and his colleagues found that certain groups of T cells tend to pair with the same types of genetically similar cancer cells no matter where they arise in a patient’s body, indicating that the immune cells are highly specialized to recognize only some cancer cells. Previous studies have seen that patients with more T cells present in and around their tumors tend to fare better and respond better to treatment.
Dr. Gordon Mills of the Knight Cancer Institute at OHSU spoke about ongoing precision oncology clinical trials and preclinical research. For example, some ovarian cancer patients benefit from a class of targeted drugs known as PARP inhibitors, and Mills and his colleagues are working on ways to extend that benefit to more patients by combining these drugs with other targeted therapies.

The molecular details of HPV-associated cancer

Fred Hutch virologist Dr. Denise Galloway presented results from her team’s studies of how human papillomavirus, or HPV, might trigger the formation of cancer. HPVs are associated with nearly all cervical cancer, as well as several other anogenital cancers and oral malignancies in women and men.

Galloway, who holds the Fred Hutch 40th Anniversary Endowed Chair, and her colleagues found that proteins involved in repairing broken DNA are affected in HPV-infected cells. Being able to faithfully repair DNA is essential to prevent a damaged cell from turning into a cancer cell; for example, the “breast cancer genes” BRCA1 and BRCA2 produce proteins involved in the DNA repair process.

Galloway and her team found that HPV infection causes a different DNA repair protein, RAD51, to lose its way in the genome, landing on pieces of DNA other than the broken section. HPV-infected cells thus can’t repair their DNA as well as they should be able to.

Those findings have therapeutic implications as well. PARP inhibitors are a class of drugs that target some parts of the DNA repair machinery and could provide an alternative form of therapy for patients with HPV-associated tumors, alone or in combination with other drugs that target DNA damage repair proteins, Galloway said.

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