New Genome Characterization Center to Focus on Proteomics Across Tumor Types

Gordon Mills, MD, PhD

Gordon Mills, MD, PhD

The University of Texas MD Anderson Cancer Center in Houston has been selected as the site for one of two new Genome Characterization Centers (GCCs) funded by the National Cancer Institute (NCI) and National Institute of Health (HHSN261200800001E). This GCC will be provided through MD Anderson Functional Proteomics Reverse Phase Protein Array Core.

“MD Anderson has been at the forefront of proteomic investigation, and it is an honor to be selected as a site for this notable center,” said Ethan Dmitrovsky, MD, provost and executive vice president of the MD Anderson Cancer Center, in a press release.¹

The GCC at MD Anderson (the other GCC will be at the Broad Institute in Cambridge, MA) will aid in molecular characterization of tumors investigated in multiple NCI initiatives using genomic, transcriptomic, and proteomic analyses. Gordon Mills, MD, PhD, chair of systems biology, and Rehan Akbani, PhD, assistant professor of bioinformatics and computational biology, will lead the efforts at MD Anderson.

This GCC will focus on using functional proteomics, the large-scale study of proteins at the functional activity level, to characterize samples of patients involved in NCI-supported trials. According to the researchers at MD Anderson, the study of functional proteomics is critical to comprehensive cancer research because it investigates how changes in protein levels and structure, which are not always shown by genetic changes, play roles in tumor development and progression.

“Studying large-scale proteomic changes will greatly aid in learning more about the causes of, and potential effective treatments for, cancers and other complex diseases,” said Akbani.

Mills also emphasized that investigating large-scale changes in the proteins will guide development of targeted therapies or “rational drug combinations” that could be tested in NCI-supported clinical trials. Reverse phase protein array (RPPA) will play an important role for this large-scale analysis of tumor samples. According to Mills, the efforts at the GCC could include as many as 25,000 patient samples, and the automated RPPA platform allows for reliable analysis of over 1000 samples using at least 150 different human antibodies at a time. Mills stated that the GCC will generate RPPA data to characterize patient tumor samples and possibly identify areas of tumor resistance or effective drug combinations.

“The [NCCI-supported clinical trials] are designed to identify biomarkers of response or resistance or to identify rational drug combinations,” said Mills. “The [RPPA] data will impact clinical trials of multiple diseases in terms of patient selection and also in terms of rational drug combinations.”

The Cancer Genome Atlas Pan-Cancer analysis project has analyzed molecular mutations at the DNA, RNA, protein, and epigenetic levels to describe similarities, differences, and themes across multiple tumor lineages.²The overall goal for this large-scale data set is to support development of pan-disease trials that investigate potentially effective therapies across multiple types of tumors. According to Mills, the large-scale analysis of data at the GCC is expected to further support development of bucket trials to evaluate the importance of biomarkers and efficacy of therapeutic options across cancer lineages. This may also allow identification and evaluation of therapies for rare cancer types or molecular aberrations that are unusual for a particular type of cancer, which will give medical oncologists more personalized options for patient treatment.

Initially, the GCC is expected to support several important NCI initiatives, including the Exceptional Responders Initiative, ALCHEMIST precision medicine trials, and the Cancer Driver Discovery Project, that aim to clarify the relationship between tumor characteristics at the molecular level and patient response to therapy. The Exceptional Responders Initiative investigates molecular factors in tumors of patients who have exceptional responses to drug treatments. Similarly, the ALCHEMIST precision medicine trials identify patients who have lung tumors with uncommon genetic alterations and evaluate their drug treatments to improve clinical outcomes. The Cancer Driver Discovery Project characterizes driver genetic events that occur in at least 2% of lung adenocarcinoma, colorectal cancer, and ovarian cancer cases and evaluates whether or not those events influenced the therapeutic response.

The GCC will also support efforts from the Division of Cancer Treatment and Diagnosis, the Cancer Trials Support Unit, and the Cancer Therapy Evaluation Program at the NCI. Mills expects the role of the GCC to evolve as NCI initiatives and programs develop over the coming years and expresses optimism about the value of this data set for improving cancer therapies for patients and medical oncologists.

“This will provide an incredible information trove linked to high-quality patient outcomes data, genomic, epigenomic, and proteomic data,” said Mills. “It’s a great example of how working together can yield important clinical understanding.”

References

1. MD Anderson press release.http://www.mdanderson.org/newsroom/news-releases/2015/md-anderson-one-of-two-genome-characterization-centers.html.Accessed July 27, 2015.
2. Weinstein JN, Collisson EA, Mills GR, et al. The Cancer Genome Atlas Pan-Cancer analysis project.Nature Genetics. 2013;45(10):1113-1120. doi:10.1038/ng.2764