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VOL. 11 | NO. 20 | Saturday, May 19, 2018

UT/West Institute’s Hayes Plays Critical Role in The Cancer Genome Atlas

By K. DENISE JENNINGS

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The Cancer Genome Atlas, a comprehensive map of the key genomic changes in 33 types of cancer, wrapped up a decade-long, $300 million national science project in April, with Dr. D. Neil Hayes, scientific director of the University of Tennessee/West Institute for Cancer Research, playing one of only a handful of leadership roles. 

NEIL HAYES (Greg Campbell)

A flagship effort of the National Institutes of Health, The Cancer Genome Atlas (TCGA) is a collaboration between the National Cancer Institute and the National Human Genome Research Institute. The project, which included 20 collaborating institutions, has produced numerous published articles in many of the top medical journals in the world. The data from the project has also been made publicly available in its entirety to help spur innovation in the development of targeted treatment for many types of cancer. 

“This project has a direct connection in all kinds of ways to the Human Genome Project (HGP) that reported its results in 2002,” said Hayes, who also serves as the Van Vleet Endowed Professor in Medical Oncology in the University of Tennessee Health Science Center’s Department of Medicine. “The idea there was to have a reference genome of what normal DNA looks like. HGP was the world’s first map of human DNA. With a reference for normal DNA, the easy thing to do would be to compare it to abnormal DNA, and cancer really is a disease, at its heart, of DNA. In every patient with cancer, their DNA is broken in some way.” 

One of the most significant results of The Cancer Genome Atlas is the recategorization of cancer by cellular pathway instead of organ type, said Hayes, who was primarily responsible for the collection and analysis of the 11,000 tumors used in the project. 

‘THE PARTS MANUAL FOR CANCER’

TCGA happened during a period of rapidly changing technology, which Hayes says was part of the fun and part of the challenge. At the same time, the ethics of cancer research also was evolving, and the manner in which tissue samples were collected was a hot topic. Although 11,000 tumors were used in the project, Hayes looked at tens of thousands of patients and tumors. 

“Less than one in 10 of the promised tissue samples made it into the project,” he said. 

West Cancer Center played a primary role in providing a large number of African-American patient samples, which were found to be underrepresented at the beginning of the project, said Dr. Lee Schwartzberg, executive director of West Cancer Center and medical director of West Clinic. Schwartzberg helped recruit Hayes to Memphis a little more than a year ago from the University of North Carolina to be the scientific director at the UT/West Institute for Cancer Research.

In addition to tissue collection, Hayes and his team were primarily involved with sequencing the RNA, which reads and implements the instructions of DNA to create proteins in the body, for all 11,000 patients. 

Through the scope and findings of the TCGA, researchers went from looking at one tumor at a time to looking across tumors and seeing what was shared, said Hayes, who loves that the acronym for the project is also a representation of the four building blocks of DNA. 

“The term (The Cancer Genome Atlas) is really an amazing term. It’s a beautiful representation of what just happened,” Hayes said. “Before we started, the DNA of cancer was a mystery, which was great because there is the potential for a lot of hope, but also scary. There is no mystery anymore. There is an atlas for cancer. We’re past the mystery phase. We have the atlas … the parts manual for cancer, which means the beginning of the end of cancer. The map is drawn.”

One of the disappointing findings of the project was that there are a minimal number of drugable mutations, which scientists had hoped would be a bigger solution to the problem of cancer. The positives are that there is no more mystery, and the problems that need to be solved are on the table, Hayes said. 

“It was possible before all this fancy stuff happened to figure things out, but it was just a lot more work,” he said. “In just a few keystrokes I can look at 10,000 patients and have an answer about a cancer gene. At 11 o’clock on a Friday night I can do things that could not even be dreamed of five years ago.” 

WHAT’S NEXT

“As with a lot of revolutions – and let’s be clear, DNA technology is as significant as the X-ray or the microscope – it takes a long time to figure out how to use them,” Hayes said. “There are many observations that are not useful. We’re a long way from having all of this information to being able to use it.” 

TCGA is a parts manual, but it didn’t actually get to look at all the parts in motion, he said. Looking at how tumors behave in different patients and connecting specific abnormalities in DNA to clinical outcomes is the next step. 

“Most of (TCGA) really looked at the genetic part, which is only about 10 percent of the genome. We still have questions about the non-coding part of the genome.”

In the near term, a discovery Hayes made about a particular genetic pathway in squamous tumors that causes them to be resistant to radiation may have clinical implications for deciding on the most effective treatment options for specific patients. 

An example is a patient with early stage larynx cancer which normally has two equally effective treatments – surgery and radiation. A patient whose tumor has a specific mutation in the pathway of the Nrf2 gene could rule out radiation, which likely would not be effective on the tumor, and choose surgery instead.

THE MEMPHIS CONNECTION

Hayes decided to move to Memphis and become scientific director of the UT/West Institute because of the potential opportunity for the advancement of adult cancer care in this area, and the clear commitment of the Memphis community to support groundbreaking research and clinical treatment of cancer. 

“Out here in the middle of the country, far from the Ivy League, this place can support the world-class cancer treatment center – St. Jude – but it clearly had a gap in adult care,” Hayes said. “There’s opportunity here, and I expect that good things can happen in adult cancer.” 

UTHSC chancellor Dr. Steve J. Schwab said Hayes’ recruitment creates opportunities for new clinical trials in Memphis. 

“Dr. Hayes is an internationally recognized investigator who leads and co-leads several national multicenter cancer care clinical trials. His recruitment to UT and the West Cancer Center brings these clinical trials to Memphis,” Schwab said. “This opens up many more investigational therapies for the people of Memphis and the Mid-South.” 

Hayes has been tasked with integrating research across UT and West Clinic and organizing the research efforts into programs, clinical research, drug development, discovery research and cell biology. 

He has identified researchers at UT and West who previously had not worked together and organized them into programs, Schwartzberg said. 

“We will use these programs as a springboard to recruit other scientists to Memphis and eventually apply for a designation as a National Cancer Institute center in the next few years,” Schwartzberg added.

Hayes said leaders at UT, West Clinic and other partners want to see growth in genetics research, and there’s enthusiasm and resources to plan and execute new programs over the next few years. 

“There’s great collaboration between the academic partners and the community leaders,” Hayes said, “and we’re going to build that vision together.”

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