Ovarian cancer is not really a silent killer. There are symptoms, but they are often mistaken for other conditions. As a result, the search continues for new biomarkers, better outcomes, and a cure.
Regardless of its widely-known nickname, ovarian cancer is not really a silent killer. There are symptoms, but they are fairly noticeable or commonly mistaken for another condition, such as irritable bowel syndrome. As a result, the search progresses for new biomarkers, more positive outcomes, as well as a cure for this life-threatening disease.
There has been recent progress in therapies: three new targeted drugs called PARP inhibitors have helped multiple ovarian cancer patients, especially those with inherited BRCA1/BRCA2 mutations, which are responsible for 15% of all ovarian cancer cases. Combinations of old and new drugs are also showing promising results. But regardless, there is still so much left to do to squelch this no-so-silent killer.
At present, researchers at Fred Hutchinson Cancer Research Center are working to solve 3 of the most problematic areas surrounding ovarian cancer:
- Early detection and screening
- Chemotherapy resistance
- Development of new treatments
Improving ovarian cancer survival rates
The fact that ovarian cancer is often diagnosed at an advanced stage, when survival rate is only 20-30%, remains one of its biggest challenges. This is why the two-minute questionnaire developed by Dr. M. Robyn Andersen with Fred Hutch and Dr. Barbara Goff with the University of Washington has been a valuable contribution. The questionnaire consists of three questions, asking a woman if she is experiencing one or more of the following symptoms that may point to ovarian cancer:
- Abdominal and/or pelvic pain
- Abdominal bloating and/or increased abdomen size
- Feeling of fullness quickly and/or inability to eat normally
Its creation has led to guidelines for assessing symptoms, which are now being used by healthcare professionals. “Prior to that work, a lot of physicians believed that ovarian cancer was a silent killer and that there weren’t symptoms. We found a very high percentage of women reported symptoms and were able to describe them in sufficient detail to make them not vague. The ovarian symptom index is one of the things I’m proudest of” said Dr. Andersen.
Women with symptoms that are frequent, persistent, and new in the past year should talk to their doctor, as they may be candidates for further evaluation with ultrasound and blood tests, such as CA-125. “Recent research indicates that approximately one in 140 women with symptoms may have ovarian cancer. Aggressive follow-up of these symptoms can lead to diagnosis when ovarian cancer can be caught earlier and more effectively treated” said Dr. Andersen.
Unfortunately, some women may not experience symptoms until the disease has reached an advanced stage. This is why Dr. Nicole Urban, head of Fred Hutch’s Ovarian Cancer Research Program, has been working for years to discover additional blood biomarkers for more effective screening of ovarian cancer. Her work has resulted in the introduction of the human epididymis 4 protein (HE4), a blood-based biomarker that can predict epithelial ovarian cancer in some women.
Other biomarker efforts continue at Fred Hutch, with studies launched by Dr. Jason Bielas and Dr. Charles Drescher, both translational researchers. The researchers are planning to use a DNA sequencing tool (CypherSeg) to detect – through a routine Pap smear – a certain rare mutation that is specific to high-grade serous cancers. High-grade serous cancers are the most common and deadly subtype of ovarian cancer and their detection would be key to successful treatment. “If successful, our proposed work will lead to a clinically useful test that will identify women who would benefit from the removal of precancerous lesions prior to the development of ovarian cancer, and thus eliminate HGSC-associated death by disease prevention” said Dr. Bielas.
Identifying chemo-resistant patients ahead of time
Once diagnosed with ovarian cancer, a majority of women undergo chemotherapy with platinum. Unfortunately, this type of therapy does not work for everyone, which means that some women undergo the exhausting and draining process with no benefit.
For this reason, Dr. Amanda Paulovich, a clinical research at Fred Hutch, aims to distinguish the patients who will not respond to standard chemotherapy from those who will – before any chemo is administered. “Fifteen to 20 percent of patients have tumors that never respond to this chemo. Their disease continues to progress. But by the time we figure this out, the patient is so sick they’re not eligible for a clinical trial. If you could predict this lack of response, you wouldn’t waste their time on chemo that doesn’t work. You’d get them into a clinical trial and find out how to treat those tumors” she said.
Proteogenomics, which utilizes a combination of proteomics with genomic sequencing, is a promising new approach to identifying chemo-resistant patients in advance. The sequencing may also be able to help identify biological information on tumor behavior, targeting patients whose tumors become resistant to chemo over time. “We have better preclinical models than we used to have, and we also have better technologies for looking at the cancer cells — in terms of the genome and the proteome. The hope is to bring the novel tools into play and see if we can have better luck than folks have had in the past” said Dr. Paulovich.
Balancing the urgency of a cure with scientific rigor
Dr. Kristin Anderson, postdoctoral research fellow at Fred Hutch and breast cancer survivor, is currently working in the Greenberg Lab and studying an approach known as T-cell therapy. This new form of immunotherapy uses specially altered T-cells to more specifically target cancer cells. Dr. Anderson has focused her efforts on testing T-cell therapy by developing a mouse model that aims to go after a protein (mesothelin) that is overproduced in some solid tumors.
Further research is expected to start in January 2019 with a combination Phase 1-2 clinical trial for patients with pancreatic cancer. Once sufficient data is collected and the safety profile is met, Dr. Anderson and fellow researchers will direct their efforts to patients with ovarian cancer. “If you infuse activated CD8 T cells in the blood, they can go anywhere. And when they recognize their target, they stay in place until they have eliminated all their targets. Some new data even suggests that T cells can divide in tissues, which may give this therapy an even greater advantage when it comes to outnumbering and eliminating tumor cells” said Dr. Anderson.