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PROTEOMICS IS AT AN INFLECTION POINT

30 Apr 2021 1:30 PM | Anonymous member (Administrator)

Written by Henry Rodriguez, National Cancer Institute, USA

Born out of the Human Genome Project, the field of genomics evolved with phenomenal speed into a dominant scientific force and opened new avenues to discover cures to diverse diseases… especially in oncology. And as quickly as genomics grew, today we again find ourselves in the midst of a new revolution in science. This new revolution is enabled by the convergence of genomics with proteomics, whose collective goals are to achieve a comprehensive understanding of the information encoded in the genetic material of organisms and how it directs the organization and function of living systems.

What we are now seeing in proteomics is a science discipline that seems to be at an inflection point, that is the result of widespread technological advances (analytical and computational, standardized workflows ensuring data rigor and reproducibility, and data sharing with the public) and an acknowledgement that genomic data alone do not always provide sufficient insights into the molecular classification of cancer in modern medicine. The outlook for proteomics has brightened substantially. And while today we assess these advances with optimism (and pessimism) as it pertains to precision medicine, the road taken to where proteomic advances are today has not been easily traveled.

At the U.S. National Cancer Institute, National Institutes of Health, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) was established to address these advances in the field of oncology. Its initial goal was to standardize proteomic methods to ensure rigor and reproducibility of large-scale protein measurements among laboratories, done in coordination with the U.S. Food and Drug Administration and the American Association for Cancer Research. Having achieved this goal, CPTAC then applied its standardized proteomics workflows to three previously genomically characterized tumor types from TCGA (proteogenomics), that revealed additional layers of molecular information not possible through genomics alone. The success of these activities by demonstrating the benefit and need of integrating proteomics with genomics to produce a more unified understanding of cancer, led the NCI to expand CPTAC’s proteogenomics tumor characterization program and for the very first time, to partner with NCI-supported clinical trials.

The reality is that proteomics and genomics are not competitors. Rather, they are partners. Together, along with other “omics” approaches, they promise to reveal molecular patterns spanning multiple layers of biology and informing new approaches to diagnostics and therapeutics. These complementary approaches stand to make precision medicine a reality.

The CPTAC program took a risk and in doing so pioneered the emerging field of cancer proteogenomics, while perhaps more importantly restoring interest and enthusiasm in the use of proteomics in the cancer community. To commemorate the advances in science made by the CPTAC program to accelerate our understanding of the molecular basis of cancer through the application of large-scale proteome and genome analysis, and the program’s commitment to creating public resources (data, assays, and reagents [antibodies]) that are utilized by the cancer research community, Cell Press has created an online space dedicated to archiving CPTAC research (https://www.cell.com/consortium/CPTAC) that has and will be published in its family of journals. Also included below are papers that are a collaboration between CPTAC and the International Cancer Proteogenome Consortium (ICPC; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002958). Collectively these papers provide strong resource-based frameworks to better understand a range of human cancers through the lens of precision oncology and will be valuable in informing effective treatment options.

Furthermore, to understand where colleagues and I see cancer research headed in the next decade, a perspective article was recently published where we examine cancer through the lens of comprehensive molecular characterization of tumors from cancer patients. In this article (https://www.cell.com/cell/fulltext/S0092-8674(21)00285-3) titled “The Next Horizon in Precision Oncology: Proteogenomics to Inform Cancer Diagnosis and Treatment,” we describe the significant contributions of The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) to multidisciplinary collaborative team science and precision oncology, and make the case that proteogenomics needs to be fully integrated into clinical trials and patient care. This approach of genomic and proteomic markers, we believe, will further enable precision oncology to deliver the right cancer treatment to the right patient at the right dose and at the right time.





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