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APOLLO Initiative Aims to Make Proteogenomics Routine Part of Cancer Treatment at VA, DoD

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NEW YORK (GenomeWeb) – The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) is collaborating with the US Department of Defense and the Veteran Affairs Veterans Health System to incorporate proteogenomics as part of cancer patient treatment regimens.

The three parties announced this month the formation of the Applied Proteogenomics Organizational Learning and Outcomes (APOLLO) Network, which aims to build a system in which VA and DoD cancer patients routinely undergo genomic and proteomic profiling with the goal of matching their tumor types to targeted therapies.

Details including funding, what facilities will perform the analyses, and what types of analyses will be used are still being worked out, Warren Kibbe, director of the NCI's Center for Biomedical Informatics and Information Technology, told GenomeWeb. Initially, the project will focus on analyzing a cohort of 8,000 lung cancer patients drawn from the VA and DoD systems.

The project fits under the larger Cancer Moonshot initiative launched this year by Vice President Joseph Biden. The Moonshot has raised concerns among some proteomics researchers who worry it will focus primarily on genomics while incorporating little proteomics work. In a statement announcing the APOLLO Network, however, organizers suggested a significant role for proteomics.

Indeed, they noted that "the main difference between the APOLLO Network and the status quo is acceleration of federal efforts in the relatively new field of proteomics. The APOLLO Network makes possible a quicker pace and higher level of resources devoted to proteogenomics, which is now the keystone to everything the VA and DoD will be doing in precision oncology."

"APOLLO will characterize and compare tumors made available through the APOLLO network to develop a deeper understanding of cancer biology, identify potential therapeutic targets, and identify pathways important for cancer detection and intervention," Kibbe said. "We think this is an ideal Moonshot project."

One of the largest ongoing clinical proteomics initiatives, CPTAC has been working for the last five years on proteogenomic analyses of cancer 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.

As such, the APOLLO project is essentially a continuation of its ongoing work.

The participation of the DoD and VA in the network, however, indicates a broadening of proteogenomics research into organizations that have had less uptake of proteogenomic approaches to date.

Genomics has traditionally dominated clinical omics work, but, Kibbe said, "it has become increasingly obvious that in order to understand the features present in the genome, epigenome, and transcriptome, we need to have data on the proteome, including post-translational modifications."

The hope is that by looking at proteomic and genomic data, researchers and clinicians can better decipher the importance of, for instance, genetic mutations. One challenge presented by modern sequencing approaches is interpreting the large numbers of genomic alterations such methods can find, distinguishing between meaningful changes that drive disease and changes that happen to be present but are not driving disease.

Integrating proteomic analyses is a possible way to do that. For instance, because proteins are the functional molecules that mediate many biological processes, a genetic mutation that leads to an actual change at the protein level is more likely to be disease-related than one that doesn't lead to protein changes.

Additionally, past studies have shown that potentially meaningful proteomic changes are not always present at the genomic level, which suggests information that could enable better targeted treatments might be missed without proteomic analysis.

Kibbe said that the APOLLO Network plans to expand from its initial lung cancer focus to look at multiple cancer types and aims "to enable better testing of clinical questions on toxicity and response, sequencing and proteomics, analysis of samples, and use of data science and analysis tools in the context of two national healthcare systems."

He said that CPTAC would be evaluating what additional cancer types to move into, basing the decision on "clinical need, patient volume, scientific opportunity, and therapeutic opportunity."

Broadly speaking, the organizers anticipate three main outcomes from the project, Kibbe said.

"The first is to have the care and research aspects of DoD, VA, and NCI build capacity and knowledge working together on state-of-the-art proteogenomics," he said. "The second is to more effectively bridge the oncology care, oncology research, and clinical trials activities of DoD, VA, and NCI, with the intent of increasing access to cancer clinical trials."

Finally, he said the effort hopes "to build on the existing evidence base available in proteogenomics with the goal of making novel observations that would inform cancer detection and inform therapeutic decisions."

Ultimately, the initiative plans to make its findings available to physicians outside the VA and DoD systems. Kibbe said that genomic, clinical, laboratory, and pathology data from the project will be shared through the NCI's Genomic Data Commons. The APOLLO Network will be designing a similar data commons for the proteomic data, he added.

Precisely what types of proteomic data and what platforms will be used to collect it remains to be determined, Kibbe said. He noted that, ultimately, "proteomic panels, such as targeted mass spec assays, will be developed to complement the genomic panels in order to improve our ability to more precisely predict response the therapies."

The network also has yet to decide what facilities will perform the analysis. The tumor characterization centers established through the CPTAC initiative would seem one obvious option, but, Kibbe said, that that detail has yet to be determined.

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