The Applied Proteogenomics OrganizationaL Learning and Outcomes (APOLLO) network is a collaboration between NCI, the Department of Defense (DoD), and the Department of Veterans Affairs (VA) to incorporate proteogenomics into patient care as a way of looking beyond the genome, to the activity and expression of the proteins that the genome encodes. The emerging field of proteogenomics aims to better predict how patients will respond to therapy by screening their tumors for both genetic abnormalities and protein information, an approach that has been made possible in recent years due to advances in proteomic technology.
Screening a patient’s proteogenome may enable researchers to more precisely match their tumor types to targeted therapies than screening for genomic mutations alone. Proteogenomics may also help researchers more completely characterize the biologic pathways of cancer development, metastasis, and treatment resistance. Multiple pilot studies have shown that, across tumor types, proteogenomics identifies additional biology, beyond standard genomics alone.
Since most cancer drugs target proteins, researchers hope that combining protein analysis with gene analysis will improve the ability to predict tumor response to treatment and, eventually, to match the tumor with the right drug.
Deepening Understanding of Proteogenomics
The APOLLO network was launched in 2016 in response to the Beau Biden Cancer MoonshotSM challenge to federal agencies to work closely together to hasten the progress of cancer research. The network speeds the pace of proteogenomics research and increases the resources devoted to it. Partnering with the nation’s two largest health systems – DoD and VA – allows NCI to study a larger number of patients and obtain results faster and more efficiently than conducting tissue-based proteogenomics and clinical trials on its own.
APOLLO is analyzing the DNA, RNA, and protein expression of 8,000 annotated human tissue specimens from a wide variety of organ sites acquired from DoD and other medical facilities. APOLLO’s first phase is underway and is focused on the full proteogenomic profiling of cancers of the lung, ovary, endometrium, prostate, and breast. APOLLO’s next phase will involve bringing the proteogenomics research workflow into the DoD and VA clinical systems in which donated patient tissue routinely undergoes genomic and proteomic profiling with the goal of characterizing both RNA and protein expression and ultimately matching tumor types to targeted therapies. In this phase, all cancer types will be studied.
The data will be derived from DoD and VA clinical trials and health care system databases and include a full set of medical images, including CT and MRI scans, obtained before and during treatment. Each set of noninvasive images can be connected to the patient’s genomic, proteomic, and clinical data.
The data will be curated and made available publicly through the Genomic Data Commons, Proteomic Data Portal, and Cancer Imaging Archive (imaging data). Using all of the data available (analytical, invasive, noninvasive, and clinical) will enable researchers to study the relationships among these data, validate results, and develop predictive and prognostic models to improve patient care.
The DoD agency leading the APOLLO network is the Murtha Cancer Center (MCC) at the Uniformed Services University of the Health Sciences (USUHS) in Bethesda, Maryland. DNA sequencing and RNA sequencing will be performed by The American Genome Center (TAGC) at USUHS. Proteomic workflows will be analyzed on multiple platforms by NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), led by the Fred Hutchinson Cancer Research Center in Seattle, Washington, and the Murtha Cancer Center’s Clinical Proteomics Platform (CPP), led by the Gynecologic Cancer Center of Excellence (GYN-COE) in Fairfax, Virginia.
The CPTAC-Fred Hutchinson resources include next-generation targeted mass spectrometry called multiple reaction monitoring (MRM). The MRM is used to develop a panel of tests to measure key proteins that can serve as markers for tumors and is now being readied for implementation in clinical trials. The Murtha Cancer Center’s proteomics discovery resources include advanced capabilities in liquid chromatography-tandem mass spectrometry for conducting quantitative assessments of proteins and their post-translational modifications in the GYN-COE lab, and a consortium of collaborators to be named this year.
The APOLLO network represents a continuous dedication to multidisciplinary research and team science that brings together leading cancer centers and organizations to study the molecular basis of cancer through proteogenomics.