Varmus Leaving NCI to Move Precision Medicine in Oncology Forward on Other Fronts

Harold Varmus, MD

Harold Varmus, MD

Harold Varmus, MD, may be stepping down as director of the National Cancer Institute (NCI) at the end of March, but in an interview withTargeted Oncology,he made it clear that he is not retiring. On April 1, he assumes a new position as Lewis Thomas University Professor of Medicine at Weill Cornell Medical College, where he will continue working to unravel the mysteries of cancer biology. Varmus has also agreed to assist the New York Genome Center as a senior associate core member in advocating for greater use of cancer genomics throughout New York.

Varmus and his colleague J. Michael Bishop, MD, received the Nobel Prize for Physiology or Medicine in 1989 for their breakthrough discovery more than a decade earlier that showed the oncogenes in retroviruses were acquired from the normal cells of a host and corrupted as the virus incorporated these proto-oncogenes into its own genome. In essence, they revealed that a cell’s normal genes are capable of transforming into cancer-causing genes, often in response to cell damage. Over the next several decades, researchers built on that seminal discovery to usher in an era of precision medicine in oncology.

“Precision medicine, at its base, is about diagnostics—people tend to forget that,” said Varmus. “What precision medicine does is allow us to frame the categorization of the disease in a new way based on the molecular properties of disease tissue. For cancer, that means looking at a cancer cell and determining why it behaves the way it does.”

Varmus added that this involves analyzing the cell for mutations, changes in gene expression, and other evidence of alterations that affect the performance of the genome.

“When we do that, we find there are commonalities among cancers that arise in different organs, and yet vast differences in some cancers that arise in the same organ.” He explained that once you have identified the genetic damage that affects cell behavior, you need to figure out how to target it. “It’s not determining that a tumor is adenocarcinoma of the lung, but is instead determining that it isEGFR-mutant lung cancer that tells you that you should do something about theEGFR,” Varmus said.

President Barack Obama has said he plans to direct $70 million in his 2016 budget to the NCI for his Precision Medicine Initiative.¹Varmus pointed out that “the president prepares his list of items for us to do, but of course he does not give out the money; Congress can choose to give some or all of the money, or they can choose to give the money but not label it with the president’s initiatives.” However, according to Varmus, the NCI had already voted to allot a substantial sum of its funds for precision medicine.

“It is in our plans to expand our efforts in basic science, informatics, and genomics.” The exceptional responder program is one example of the NCI’s efforts to advance precision medicine. “In the past, most trials were done by pooling patients who have a cancer that arises in a certain organ, like bladder cancer or lung cancer or brain cancer. Those patients represent a very heterogeneous mix, and many of those participants had cancers that were very different from the others,” Varmus said.

He compares these early trials to conducting a clinical trial for pneumonia, which can be caused by different strains of bacteria, without wondering what the bacterium was. “What you want is a precise diagnosis. In this case, we are going back to the old trials and looking for patients who had a beneficial effect from a drug in a study in which the drug generally didn’t work. We’re taking those tumors, when available, and looking at those genetic abnormalities and trying to figure out why it worked.” Varmus said that the NCI has received material for more than 100 patients thus far.

In a letter to the NCI community announcing his resignation as director, Varmus mentioned the “fiscal duress” he faced during his 5-year tenure.²President Obama recently submitted his proposed 2015 budget for the National Institutes of Health to Congress for consideration, which includes a small increase for the NCI. When Varmus was asked how it might affect oncology research programs should Congress not grant the full amount President Obama has requested for the NCI’s 2015 budget, he said, “We need money to do these things, so obviously the dilemma for us would be how much obligation are we under to do what the president asked us to do if we don’t get the extra money to do it?”

In dealing with ongoing budget challenges over the past 5 years, Varmus and his team strived to make the NCI more efficient, improve the grant-making process, and further the agency’s mission of advancing cancer research and reducing the burden of cancer worldwide. For example, Varmus launched the Provocative Questions initiative, which bestows grants on researchers searching for an answer to any of 24 important questions about cancer. Answering just one of these questions could lead to tremendous advances in the understanding of cancer, but because the rewards may be less immediate, research on these topics is poorly funded, according to Varmus.

Although CRISPR technology is not a result of the Provocative Questions program and has applications beyond oncology, Varmus likes to use CRISPR as an example of “something that was totally unexpected, made possible by making an investment in an abstruse biological phenomenon.” He added, “CRISPR probably would not have been studied if some enlightened funding agency was going to make an investment.” Under Varmus, the NCI also established the NCI Center for Global Health, to support cancer research in low- and middle-income countries; the Center for Cancer Genomics; and the Outstanding Investigator Award, a 7-year grant designed to provide investigators with greater stability in pursuing their work.

The NCI continues to collaborate with the private sector on important initiatives. “We have numerous collaborations in this industry. Some are run through a third party, like the Foundation for the NIH. Some are arranged through profit and research development agreements,” Varmus said. “We have a well-known trial called MATCH that is going to depend on donations of drugs from companies. We have another trial that was launched some months ago through the NIH called the Lung-MAP study, which involves genetic analysis for squamous cell carcinoma. Companies have put up much of the funding for it; the Foundation for the NIH put up some of the money, and the research sites will be contributing.”

Throughout his storied career in oncology, Varmus has left a trail of successes. His departure from the NCI will no doubt be a loss for the agency. Fortunately, however, the world will continue to benefit from his ongoing involvement in oncology research and his advocacy for more research funding, collaboration, and openness; and for more precise medicine that will ultimately lead to improved outcomes for patients with cancer.

References

1. Fact sheet: President Obama’s Precision Medicine Initiative. http://www.whitehouse.gov/the-press-office/2015/01/30/fact-sheet-president-obama-s-precision-medicine-initiative. Published January 30, 2015. Accessed March 6, 2015.
2. Varmus H. A letter to the NCI community. http://www.cancer.gov/aboutnci/director/messages/harold-varmus-resignation. Published March 4, 2015. Accessed March 5, 2015.