Proteogenomics Drives Novel Ovarian Cancer Diagnostic Approach
A 64-protein pattern could identify which patients would or wouldn’t benefit from standard ovarian cancer treatments
SEATTLE, WA — Despite advances in surgery and chemotherapy, the survival of people with certain types of ovarian cancer has not significantly changed in decades. Some ovarian cancer patients go through treatments that don’t work since it’s not clear before treatment which tumors will respond.
A new study published in Cell and led by scientists at Fred Hutchinson Cancer Center (Fred Hutch) and the Winthrop P. Rockefeller Cancer Institute points toward a potential diagnostic that, once adapted for the clinic, could identify patients with types of ovarian cancers that would be refractory or unresponsive to standard treatments.
“We now have a potential 64-protein predictor that identifies upfront—before they get treatment—about 35 percent of patients with refractory disease at a very high specificity,” said Amanda Paulovich, MD, PhD, a Fred Hutch physician-scientist who holds the Aven Foundation Endowed Chair. “If we can identify patients who are unlikely to respond to standard treatment, clinicians could help them pursue a clinical trial instead.”
Paulovich and her collaborators focused on a subtype of epithelial ovarian cancer, called high-grade serous ovarian cancer (HGSOC), which accounts for the most deaths from ovarian cancer and for which treatments have not improved survival in decades. “Right now, we can’t identify these ovarian cancer patients upfront. We find them by default: They get sick and pass away so quickly that they can’t even be put on new clinical trials,” said co-senior author Michael Birrer, MD, PhD, who directs the Winthrop J. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences. “This study is a huge step forward in that.”
“These tumors have a complex phenotype, so there’s no one single biomarker that distinguishes them and identifies which treatment they’ll respond to,” said Paulovich. “Most diagnostics that exist today are built around one biomarker, but for a complex situation like ovarian cancer treatment response, we need a multiplex diagnostic.”
Large-scale proteogenomics to the rescue
Paulovich has built her Fred Hutch lab around developing assays that can measure thousands of proteins and genetic markers in tumors, a field called proteogenomics. She and her research team use mass spectrometry and computational approaches to discern patterns in large numbers of proteins and genes, which could distinguish patient tumors and how they would respond to treatment.
In the Cell study, the team characterized proteins and genetic markers in 242 HGSOC samples that responded or did not respond to treatment. The tumor samples were collected from patients before they began treatment.
In addition to discovering the 64 proteins that best-signified tumors resisting standard initial treatment with platinum-based chemotherapy, the team identified five different types of HGSOC tumors that seem to be driven by different biological processes. The molecular changes at play in these newly defined ovarian tumor subtypes may well hold clues for scientists seeking targets for future targeted treatments and bring new treatment options for patients with chemotherapy-refractory disease.
- This press release was originally published on the Fred Hutch Cancer Center website