Genomic Research Fuels Innovation at Johns Hopkins

By Ed Rabinowitz
Published: Wednesday, May 19, 2010
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It is often said that to be successful, it is important to stick to your knitting. In other words, focus on doing what you do best. At the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, physician researchers do just that.

Since its inception in 1973, the Cancer Center has been dedicated to improving our understanding of human cancers and finding more effective treatments. One of only 40 cancer centers in the country designated by the National Cancer Institute as a Comprehensive Center, researchers at the institution have been characterizing the acquired genome defects in cancers for the better part of the past few decades. And according to William Nelson, MD, director of the Kimmel Cancer Center, they have gotten very good at it.

“I think the real challenge is going to be how we harness this incredible body of information,” Nelson said. “What is [the body of information] going to mean for how you can best be treated with what everyone anticipates will be this evolving portfolio of targeted agents that are somewhat different than drugs we’ve used in the past? I think that’s a challenge that we are very well positioned to meet.”

Eradicating dandelions

Richard Jones, MD, professor of oncology and director of Bone Marrow Transplant, explained that there are cancer drugs available that are very effective at placing patients in remission; the problem is that patients do not stay in remission. The hypothesis behind those relapses is the existence of cancer heterogeneity. In other words, there are cancer cells that are sensitive to treatments and other cancer cells that are highly resistant. The latter—referred to as cancer stem cells—are what lead to relapse. Jones uses a metaphor that works scientifically and in explanations to patients: Cancer is a dandelion.

“Cancer is heterogeneous, with the bulk of the cancer being the part of the dandelion you can see, and the cells responsible for the growth of the cancer are the root, or the cancer stem cells,” Jones explained. “We’ve developed a lot of lawnmowers with our treatments, but we all know what happens if you just mow the dandelion [down]. It’s eventually going to grow back.”

Jones and his colleagues are actively studying how cancer stem cells operate in a variety of malignancies, including leukemia, ovarian cancer, and breast cancer. The Cancer Center has several clinical trials underway, Jones said. He explained that they are looking for treatments they can bring in to “get rid of the root once the weed [has been] mowed.” The challenge, according to Jones, is that just like the roots of the dandelion, these cancer stem cells are biologically quite different from the rest of the tumor being treated. However, they might not be that different from one another.

“What allows us to characterize a plant is the plant itself,” he explained. “It’s the same thing in cancer. Breast cancer cells look like breast cancer; leukemia looks like leukemia. But the cancer stem cells in these disorders look a lot more like each other, just like the roots of a tulip and the roots of another plant. It’s very possible that these treatments that we’re using to target one type of cancer stem cell are going to be active against other cancer stem cells.” If that happens, he said, “We may be looking at truly a cure for cancer, not just a cure for breast cancer or leukemia.”

Next generation sequencing

Researchers at the Kimmel Cancer Center are poised to use a new technology called next generation sequencing to dramatically improve the battle against cancer. According to researcher Bert Vogelstein, MD, Clayton Professor of Oncology and Director of the Ludwig Institute at the Johns Hopkins Kimmel Cancer Center and Investigator, Howard Hughes Medical Institute, next generation sequencing harnesses the most advanced technologies in imaging, optics, molecular biology, chemistry, computer science and engineering to make analyzing genetic alterations in tumors more feasible, faster, and for less money.

Vogelstein said that at the start of 2010, there were 73 tumors throughout the world in which all of the genes had been sequenced. When the process of sequencing first began several years ago, it cost an estimated $150,000 to $200,000 to do so for each patient. Using today’s next generation sequencing technology, that cost has been reduced tenfold, to roughly $20,000. And what used to take about a month now takes a matter of days.

“The real breakthrough is the ability to [gene sequence] at a cost that will eventually be affordable in a clinically applicable way,” said Vogelstein, noting that the next generation sequencing instrument costs roughly $500,000, and the computers that collect the data add another $200,000. “In a couple of years, today’s cost will undoubtedly come down to something like $1,000 or $2,000, and then it will be in the range of other sophisticated patient tests like MRIs.”

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