SCIEX, a life science technology company based in Framingham, Massachusetts, announced this week a collaboration agreement with the Fred Hutchinson Cancer Research Center laboratory of Dr. Amanda Paulovich to make targeted proteomics in cancer research more reproducible and specific.
The technique developed by Paulovich and colleagues, called multiple reaction monitoring, or MRM, mass spectrometry, is an efficient, high-powered, precise method to detect and measure proteins in biological samples. The technology offers the potential to overcome a serious challenge in biomedical research: a lack of reliable, standardized tests for studying human proteins.
Proteins carry out most biological functions in the body – including driving cancer growth – and are the targets of most drugs. However, a lack of robust assay platforms for studying proteins has rendered the human proteome largely inaccessible to clinical research, which is an obstacle to developing novel diagnostics and therapeutics.
Widely available MRM-based proteomics assays, Paulovich envisions, will transform research by increasing the reproducibility of preclinical research and greatly advancing the development of precision-medicine approaches to detect and treat cancer.
By collaborating with the Paulovich Laboratory, SCIEX will offer researchers an “off-the-shelf” format for technology to quantitatively measure phosphorylated and unmodified proteins that are associated with cancer-signaling pathways.
“SCIEX has a long history in quantitative mass spectrometry … we are very excited about this collaboration,” said Paulovich, whose laboratory is a member of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium.
For her work in this area, Paulovich, an oncologist and cancer geneticist in Fred Hutch’s Clinical Research Division, will receive the 2015 Distinguished Achievement on Proteomic Sciences Award at HUPO 2015, the annual meeting of the Human Proteome Organization, this weekend in Vancouver, Canada.
Dr. Anne McTiernan, cancer prevention expert in the Public Health Sciences Division at Fred Hutch, was on an international panel of scientists that conducted a systematic literature review on the association between nutrition, obesity and kidney cancer.
The new report, announced Sept. 15 as part of the Continuous Update Project of the World Cancer Research Fund International, found strong evidence that being overweight or obese increases the risk of kidney cancer.
The report also found strong evidence that being tall increases one’s risk of kidney cancer, possibly in part due to developmental factors in the womb or during childhood and adolescence. This increases to six the number of cancers linked to height.
“This report, which is the most rigorous, systematic, global analysis of the scientific research currently available on diet, weight, physical activity and kidney cancer, clearly shows an association between overweight, obesity and risk of developing kidney cancer,” McTiernan said.
The analysis included almost 10 million people, of whom 15,000 developed kidney cancer.
“For each five-unit increase in body mass index [weight corrected for height] there was a 30 percent increase in the risk of developing kidney cancer,” she said.
CypherSeq, a new method developed by Fred Hutch’s Dr. Jason Bielas to accurately detect unique mutations in specific areas of the genome, is 100 to 1000 times more sensitive than other approaches. In a study published online in Nucleic Acids Research, Bielas and his team demonstrated that they could accurately detect a single gene, which carried a hallmark cancer mutation, among millions of unmutated versions of the same gene.
“CypherSeq has very broad applicability,” said Bielas, a researcher in Fred Hutch's Public Health Sciences and Human Biology divisions who studies the implications of nuclear and mitochondrial mutations in cancer development. Bielas plans to apply the technique to problems as wide-ranging as cancer-risk stratification and early detection. He also aims to use it to better understand how exposure to certain mutagens — like cigarette smoke — leads to cancer.
Bielas and Drs. Jessica Bertout and Mark Gregory, postdocs in his lab, put CypherSeq through its paces by employing it to detect rare mutations in a gene called p53, which is mutated early in ovarian cancer. They were also able to paint a picture of the spectrum of mutations that arise in yeast cells, either spontaneously or after exposure to a mutagenic chemical.
Bielas and his team are working to apply CypherSeq to detect ovarian cancer in its earliest stages based on cells from a Pap smear. One study using a less-sensitive method could detect mutated ovarian cancer cells in Pap smears from about 40 percent of women with advanced disease. Bielas thinks CypherSeq has the potential to raise the detection rate to 100 percent — and to detect ovarian cancer at its earliest stages. “We are hopeful that our enhanced method could be used to detect previously undetectable ovarian cancer, earlier, and at a stage when surgical intervention is curative,” he said.
Bielas hypothesized that with the ability to catch incredibly rare mutated cells, CypherSeq could also be applied so that oncologists could use hallmark mutations to identify cancer cells shed from a broad range of tumors in blood samples. It might then be possible to detect many tumors in the earliest stages or detect a recurrence long before worrisome symptoms appear and when treatment options have the most potential to increase survival.
Methods to detect very rare mutations — like those that occur in the rare cancer cell shed from a tumor into the blood, or the random mutation that each cell will pick up as part of normal DNA replication — were previously impossible to track with next-generation DNA sequencing, as the methods themselves are error-prone. Previously, researchers found ways to overcome this error rate to a degree — allowing them to pick out the mutated cell from about 5,000 other cells, for example. But most unique mutations, whether or not they are a hallmark of a tumor cell, will be much rarer. But now, these mutations are detectable by CypherSeq.
“[With CypherSeq] we have the ability to sequence with essentially zero errors, and we can enrich ‘target sites’ within the genome,” Bielas said. This ensures that, when hunting for mutations arising from cancer cells, “we only measure those that originate from the tumor,” he said.
Dr. Katherine Tarlock, a pediatric oncologist at Fred Hutch, on Wednesday received a $150,000 Hyundai Young Investigator Grant through Hyundai Hope on Wheels, a nonprofit supported by donations from more than 800 U.S. Hyundai dealers.
Tarlock, who studies childhood leukemia, received the grant during a ceremony at Fred Hutch attended by local Hyundai dealers.
“Children with high-risk and relapsed acute myeloid leukemia have a poor prognosis, and new treatments are urgently needed,” she said. “The research supported by Hyundai Hope on Wheels will allow us to identify potential targets for therapeutic intervention in pediatric AML, which we hope will lead to better treatments and outcomes.”
Tarlock is among many recipients across the U.S. to receive a 2015 Hyundai grant. In all, Hope on Wheels will award $10.5 million in research grants in this month in honor of National Childhood Cancer Month.