Research conducted at Pacific Northwest National Laboratory holds promise for better treatment eventually of one of the most deadly forms of cancer for women.
“We are really hoping that this work will give ovarian cancer patients hope,” said Karin Rodland, chief scientist for biomedical research at PNNL and chief author of a study published June 29 in the journal Cell.
Ovarian cancer accounts for just 3 percent of all cancers in women, but is the fifth-leading cause of cancer deaths among women in the United States.
Researchers at PNNL, with colleagues at Johns Hopkins University, are looking at ways to better identify the biological factors defining the 70 percent of ovarian cancer patients who suffer from the most malignant form of ovarian cancer, called high-grade serous carcinoma. Only one in six patients survives at least five years beyond diagnosis.
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Research could lead to better treatments or information about what treatment might work best for each patient.
Historically, cancer and its treatment have been looked at through a collection of the cancer’s genetic data, or its genome, Rodland said.
But PNNL and Johns Hopkins take the research for ovarian cancer a step further to look at how the genetic program is carried out within cells.
Adding the information about the proteome on top of the genome provides an entirely new dimension of information.
Karin Rodland, PNNL chief scientist for biomedical research
Proteins are the workhorses within the cells, performing its functions, and by combining information about the proteins, or proteomics, with genomics, researchers can develop a better understanding of the progression of cancer.
A hallmark of cancer is that too many proteins are performing harmful activities and not enough are doing helpful activities, but the sets of proteins involved are specific to different types of cancers.
Researchers at PNNL relied on state-of- the-art, scientific mass spectrometers at the Environmental Molecular Sciences Laboratory on the PNNL campus in Richland to identify 9,600 proteins in ovarian cancer cells and narrow their study to those proteins common to all of the cells studied by the teams at both PNNL and Johns Hopkins.
At PNNL, researchers focused on 84 tissue samples from ovarian cancer patients based on how long patients survived.
“We examined the data for the shortest-surviving patients and the longest-surviving patients, hoping to pinpoint biological factors associated with extremely short survival or better-than-average, longer survival,” Rodland said.
The information could lead to better drugs to treat ovarian cancer by targeting individual proteins, and it also could help personalize the treatment.
For some women, an improved understanding of the disease could allow them to skip what’s now the first type of chemotherapy traditionally prescribed for ovarian cancer and try other therapies under development. Doctors know do not have reliable ways of knowing who will need other therapies beyond trial and error.
Some patients may endure the harsh side effects — including a suppressed immune system, nausea and loss of hair — of the type of chemotherapy that’s traditionally tried first for ovarian cancer, only to find that it had no benefit for their case.
Just like anything in medicine, clinical validation will be a long and rigorous process.
Daniel W. Chan, Johns Hopkins University School of Medicine
“We’re trying to identify women who could benefit from enrolling in clinical trials earlier rather than later because they are not going to respond to the standard of care,” Rodland said.
Johns Hopkins took a different approach, selecting 122 tissue samples with genes that behaved like the BRCA1 and BRCA2 mutations already linked to breast and ovarian cancer risk and severity.
Known treatment for BRCA mutations might also work for them, or the research could lead to new treatments.
“Adding the information about the proteome on top of the genome provides an entirely new dimension of information,” Rodland said.
The combined proteomic and genomic study of ovarian cancer is in its early stages.
“Just like anything in medicine, clinical validation will be a long and rigorous process,” said Daniel W. Chan, who led the team at Johns Hopkins University School of Medicine.
The next step in the research is to validate laboratory results by looking at a new set of tissue samples collected from women newly diagnosed with ovarian cancer.
The work that is being started now through a consortium of the National Cancer Institute, which also paid for the PNNL and Johns Hopkins study.