SEATTLE — June 27, 2017 — A team of scientists at Fred Hutchinson Cancer Research Center will lead an initiative launched today by the National Cancer Institute to advance the use of targeted proteomics and genomics in the most lethal gynecological malignancy, ovarian cancer.
The new Proteogenomic Translational Research Centers (PTRC), established by the NCI’s Office of Cancer Clinical Proteomics Research (OCCPR), involves teams of researchers and oncologists across the U.S. and aims to integrate proteomics with genomics (“proteogenomics”) into NCI clinical trials.
“We envision that PTRCs will collaborate with NCI-sponsored clinical trials to expand/deepen our knowledge of drug response and resistance, ultimately improving our understanding of the cancer and tumor proteome,” said Dr. Henry Rodriguez, director of OCCPR.
At Fred Hutch, Dr. Amanda Paulovich is co-principal investigator of a team that will use recent technological advances in collecting and analyzing massive proteogenomic data sets to find ways to better match ovarian cancer patients with treatments that will work.
“Despite advances in chemotherapy and surgery, the overall survival of patients with ovarian cancer has not significantly changed in decades,” said Paulovich, a member of the Clinical Research Division at Fred Hutch. “This is because drug-resistant cancer cells enable tumors to keep growing.”
Some 239,000 women are diagnosed and 152,000 die around the world each year from ovarian cancer, according to the World Health Organization’s GLOBOCAN project.
About 20 percent of women with ovarian cancer are resistant to the standard of care, a platinum-based chemotherapy.
“Ovarian cancer by nature is often diagnosed at a late stage. Unfortunately, there’s no way to know ahead of time whether the initial treatment will work,” said Dr. Michael Birrer, co-principal investigator with Paulovich on the new grant. Birrer is an ovarian cancer doctor who has more than 30 years of clinical trial and translational research experience. He leads the gynecological cancer program at Massachusetts General Hospital, and later this year will become director of the University of Alabama at Birmingham Comprehensive Cancer Center.
“If the treatment doesn’t work the patients can be left too sick to participate in a clinical trial,” Birrer said. “This project has the potential to identify biomarkers to predict these patients and to identify pathways that will provide novel therapeutic targets.”
Previous studies have tried to find a predictor of treatment response and have failed, possibly because they were looking at only the genome or were only able to look at one protein at a time, Paulovich said.
“There’s no one mechanism of resistance; we’re going to look at the entire network of proteins and genes that together have a role,” said Paulovich, who’s also a professor of medicine in the Division of Oncology at the University of Washington School of Medicine.
She and her collaborators believe that technological advances in large-scale proteogenomics that can look at many biological markers at once will be able to reveal how a particular person’s tumor resists chemotherapy.
“I am very excited about the talented team we’ve put together for this important project,” Paulovich said. Co-investigators on the team are:
- Mayo Clinic: Drs. Scott Kaufmann, John Weroha and Larry Karnitz
- Massachusetts General Hospital: Dr. Steven Skates
- Icahn School of Medicine at Mount Sinai: Drs. Pei Wang and Eric Schadt
- Harvard Medical School: Dr. Steven Gygi
- University of Washington School of Medicine: Dr. Andrew Hoofnagle
For the new five-year project, Paulovich and her collaborators will first develop large-scale proteogenomic data on ovarian tumor samples and identify which proteins are linked to chemotherapy resistance. Then Paulovich’s lab will develop targeted proteomic assays, or tests, that measure the tumor proteins of interest. The researchers will use the biological assays they’ve developed in clinical trials with ovarian cancer patients.
“The goal at the end of five years is to know if there’s a signature that we can use to determine who will respond to platinum-based chemotherapy,” Paulovich said. “It would be great if we also are able to identify new possible therapeutic targets to help overcome treatment resistance.”
In a different project announced earlier this year, her lab is developing assays for measuring proteins important for immunotherapies. These assays initially will be tested in lung cancer, but they may be applicable to many cancer types.
Since 2007, Paulovich’s lab at Fred Hutch has been a part of NCI’s Clinical Proteomic Tumor Analysis Consortium, or CPTAC, which supports proteogenomics research collaborations across the U.S.
“Proteogenomics has great potential to unleash new insights in oncology,” said Rodriguez of the NCI. “The combination of proteomic, transcriptomic, and genomic data can now reproducibly identify proteins in cancer genomes that were difficult or not possible to infer by genomics alone.”