Dan L Duncan Comprehensive Cancer Center
Dan L Duncan Comprehensive Cancer Center

The Office of Cancer Clinical Proteomics Research announced today its multi-institutional program to further the convergence of proteomics with genomics, or “proteogenomics,” to better understand the molecular basis of cancer and accelerate research in these areas by spreading research resources within the scientific community. Among these participating Proteogenomic Translational Research Centers (PTRCs) is the Lester and Sue Smith Breast Center, part of the NCI-designated Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, the only site executing these tasks in the South.

Bringing centers together under CPTAC

The announcement of the PTRCs builds on the recently launched Proteome Characterization Centers (PCCs) and Proteogenomic Data Analysis Centers (PGDACs), which comprehensively characterize biospecimens and integrate/analyze resulting proteogenomic data to extrapolate cancer knowledge.

Baylor also has been awarded as a PGDAC site.

These three variations of proteogenomic centers of excellence (PCCs, PGDACs, and PTRCs) form the interdisciplinary pillars of the NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), which centers on using the analysis of genomic and proteomic data to eventually help solve clinically relevant cancer questions, such as drug response and drug sensitivity.

“This is an emerging method of collaboration,” said Dr. Bing Zhang, professor in the Lester and Sue Smith Breast Center and the Department of Molecular and Human Genetics at Baylor. “The CPTAC program encourages and allows multiple institutions to come together to share and contribute varied types of data, which is then studied and analyzed in a cooperative, mutually beneficial way.”

Data generation and clinical implications through PTRCs

The Proteogenomic Translational Research Center at Baylor is jointly run by the Broad Institute and focuses on breast cancer specifically. The two institutions, and other PTRCs, will be working to generate and analyze proteogenomics data to further understand the behavior and functions of cancer cells in the advancement of precision oncology.

“In the past, there has been an information gap between the data generation and the clinical implications,” said Zhang, who is a McNair Scholar. “The creation of the PTRCs addresses that gap, linking the molecular data with the clinical data.”

The PTRCs will apply proteogenomics to questions of toxicity and resistance in clinical trials, using NCI-sponsored clinical trial samples.

“Proteogenomics has great potential to unleash new insights in oncology. The combination of proteomic, transcriptomic, and genomic data can now reproducibly identify proteins in cancer genomes that were difficult or not possible to infer by genomics alone,” said Dr. Henry Rodriguez, director of the Office of Cancer Clinical Proteomics Research of the National Cancer Institute, National Institutes of Health. “We envision that PTRCs will collaborate with NCI-sponsored clinical trials to expand/deepen our knowledge of drug response and resistance, ultimately improving our understanding of the cancer and the tumor proteome.”

“As a Proteogenomic Translational Research Center, we are transitioning the proteogenomics technology and bioinformatics into clinical utility, giving us a deeper look at what the cancer cells are doing in patients,” said Dr. Matthew Ellis, director of the Lester and Sue Smith Breast Center and co-PI for the PTRC at Baylor. “The ability to access the clinical trial samples from the NCI will help us achieve big wins in cancer research in big populations, as opposed to smaller wins in more limited populations.”

Data analysis through PGDACs

Whereas the Proteogenomic Translational Research Centers integrate clinical trial data and clinical implications, the Proteogenomic Data Analysis Centers focus on applying algorithms and computational tools to develop proteogenomic data to help the NCI expand its study of clinical trial and tumor samples beyond the existing colon, breast and ovarian cancers.

“The establishment of the Proteogenomic Data Analysis Center at Baylor is a truly exciting development for our proteomics group,” said Dr. Anna Malovannaya, assistant professor in biochemistry and molecular biology at Baylor. “Cancer is a multifaceted disease, where personalized molecular medicine is not only much needed, but also attainable, given the right diagnostic tools. It is now clear, in large part due to research performed in CPTAC laboratories, that integration of genomic and proteomic characterization, rather than either discipline alone, propels our ability to understand the underlying etiology of this complex disease.”

As Baylor is both a Proteogenomic Data Analysis Center and Proteogenomic Translational Research Center site, the physical proximity of the facilities and research teams is beneficial to the project, encouraging integration among groups of scientists.

Proteogenomics and advancing precision oncology

The CPTAC program is the largest effort in the nation to advance precision medicine through proteogenomics, added Zhang. Through the PTRC and PGDAC sites, Ellis, Zhang and their team members will develop novel bioinformatics infrastructure for the integrative analysis of cancer genomic and proteomic data to advance cancer research and clinical care.

“Proteogenomics will soon lead the discussion in cancer treatment,” continued Zhang. “We will analyze the genomic and proteomic data from individual tumors in order to determine what and how to target within the tumor, thereby allowing us to provide highly specialized care.”

Proteogenomic analyses, where Zhang’s group has done pioneering work, require momentous bioinformatics effort and innovation to help researchers sift through the wealth of ‘next-generation’ data and pinpoint only the most critical, causal and targetable molecular events, explained Malovannaya, also the academic director for the Mass Spectrometry Proteomics Core. “We are looking forward to being a part of CPTAC through these new consortium centers, and to fully utilizing Baylor’s proteomics, informatics and clinical expertise in transforming cancer research,” Malovannaya said.

“It’s an entirely new way of looking at clinical specimen to drive therapies,” said Ellis, who also is a McNair Scholar. “Not only are these centers executing very exciting work, but Baylor is the only site involved in this project our region, with speaks to its strengths in both clinical and bioinformatics areas.”