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Cancer Moonshot Project Leaving Proteomics Behind, Researchers Worry

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NEW YORK (GenomeWeb) – With a planned $1 billion in funding behind it, the National Cancer Moonshot should prove a boon to cancer research and researchers.

Concerns have arisen, though, regarding the potential for the project to duplicate efforts already ongoing or to squander resources due to a lack of clear organization and focus.

And, among some proteomics researchers, there is a fear that their discipline will be shunted aside in favor of more established approaches like genomics. While the areas of focus for the Moonshot project are still being worked out, there is relatively scant mention of proteomics in public documents detailing the effort and its leadership.

"We look at the Moonshot project, and we don't want the rocket to take off without there being some proteomics payload," George Mason University researcher Emmanuel Petricoin told GenomeWeb.

Last month, Petricoin and Thomas Conrads, associate director of science technologies at Inova Health Systems' Center for Personalized Health, published an editorial in Clinical Cancer Research advocating that proteomics comprise a significant portion of the project.

"While we are extremely enthusiastic about the goals of the program, it is time we meet this revolutionary project with equally bold and cutting-edge ideas," the authors wrote. "It is time we move firmly into the post-genome era and provide the necessary resources to propel and seize on innovative recent gains in the field of proteomics required for it to stand on equal footing in this narrative as a combined, synergistic engine for molecular profiling."

More than just a discrete project, the Moonshot is an "opportunity to think about the biology of cancer and what proteomics can do in that context," Petricoin said, adding that, "at a fundamental level, cancer is a proteomic disease, and because of that we should really think about how we should rationally fund the field of proteomics in that context."

The concern that genomics is shouldering proteomics aside is not a new one for the field, and genomics has undoubtedly received significantly more funding over the years. In their editorial, Petricoin and Conrads cite a Battelle Technology Partnership for United Medical Research report that puts the amount of US federal government investment into genomics between 1988 and 2012 at around $14.5 billion. Meanwhile, previous estimates from GenomeWeb based on National Institutes of Health grant information have put annual expenditures on proteomics in the $130 million range.

As Petricoin described it, the field currently suffers from something of a chicken-or-the-egg problem. To win increased funding, proteomics needs to demonstrate clinical promise, but increased funding is required to support the sort of technology development and translational research efforts the field needs to reach its clinical potential.

That said, the field has made progress toward the clinic in recent years — enough so that it should have a significant role in clinically focused efforts like the Moonshot, Petricoin suggested.

"There are platforms and methodologies that are actually ready for prime time and are being used in clinical trials today," he said. "And they shouldn't be ignored. They should be incorporated."

As a patent holder on one such technology, the reverse phase protein array (RPPA), and a co-founder and shareholder of clinical proteomics firms including Theranostics Health and Perthera, Petricoin has more than a passing interest in driving an increased clinical role for proteomics.

He has also participated in several clinical trials where proteomics has been shown to be of value. In the I-SPY-2 trial, for instance, he and his colleagues identified several proteomic and phosphoproteomic markers that appeared useful for predicting the response of breast cancer patients to Puma Biotechnology's tyrosine kinase inhibitor neratinib.

And, in the Side-Out breast cancer study, researchers found that molecular information, including RPPA data, could help guide therapy in patients who had exhausted standard treatment regimens.

Mass spec technologies have also made notable advances in recent years, with companies including Applied Proteomics and Integrated Diagnostics marketing cancer biomarker panels that were either developed using mass spec or are offered commercially on mass spec platforms.

Nonetheless, cancer proteomics has yet to notch an overwhelming clinical success, a failure that Petricoin attributed at least in part to the field's traditional place in genomic's shadow.

"We haven't been able to create room at the table," he said. "The table is still dominated by the genomics approach, and we can't squeeze in."

Henry Rodriguez, director of the National Cancer Institute's Office of Cancer Clinical Proteomics Research, suggested that proteomics might make room for itself as a complement to genomics.

"There still is a lot of missing biology when trying to reliably predict which patients’ tumors respond to any given therapy, since only a small subset of tumors predicted to respond based on genomics actually do so — with tumor responses often being temporary," he told GenomeWeb. "I think this is one of several important areas where proteomics, in tandem with genomics — proteogenomics — can make an impact in providing a new level of molecular analysis for better cancer patient treatment decisions."

"We know that molecular drivers of cancer are derived not just from DNA, but also from proteins," he added. "It is ultimately the proteins that carry out most of the biological functions of cancer cells, and the vast majority of our cancer treatments target proteins. Thus, knowing the downstream effects of gene alterations should enable better prediction of a tumor response to a specific, targeted therapy. Blending proteomics with genomics in a clinical trial research setting, I believe will provide a new level of molecular analysis for better cancer patient treatment decisions."

Rodriguez heads one of the largest ongoing clinical proteomics initiatives, the NCI's Clinical Proteomic Tumor Analysis Consortium, which in its second stage has taken a proteogenomic focus with participants performing protein biomarker discovery and verification studies in tumor tissue samples previously characterized at the genomic and transcriptomic level by the NCI's Cancer Genome Atlas (TCGA) team. 

The initiative's third stage, which is slated to start this year and continue through 2021, will continue this proteogenomic bent while also moving in a more translational direction with the establishment of three Proteogenomics Translational Research Centers (PTRCs) that will aim to use genomic and proteomic data to better understand patient drug response and the development of resistance.

Inova's Conrads lauded the initiative's move in this direction, but said that more resources were needed to encourage the participation of proteomics researchers in translational efforts like clinical trials.

And, for those concerned about proteomics funding, the overall CPTAC trendline is not particularly encouraging. The initial five-year initiative received $104 million while the second stage of the project received between $75 million and $120 million. The third stage is slated to receive around $65 million over its five-year run.

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