NCI Director Assesses Barriers to Faster Progress in Cancer Research

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We are at an unprecedented time in our ability to turn our understanding of cancer into major clinical advances. Yet, it is a sobering time because medical research is hindered by financial shortfalls.

—Harold E. Varmus, MD

At a National Press Club media event in Washington, DC, on September 25, 2012, National Cancer Institute (NCI) Director Harold E. Varmus, MD, addressed a group of 75 reporters and officials. His discussion focused on impediments—biologic, economic, institutional, and cultural—to faster cancer research. In Dr. Varmus’s introduction, he noted that over the past 40 years, NCI has spent about $90 billion on research, yet cancer stubbornly remains a leading cause of death in the United States.

Vital Role of Government

“The NCI has been in existence since 1937, so we’re celebrating the Institute’s 75th anniversary. It is the first of the so-called “categorical” institutes and centers, which means that it is devoted to a specific disease or type of medical condition,” Dr. Varmus began, adding that there are now 27 institutes and centers.

Dr. Varmus stressed that the NCI exemplifies the vital role government plays in bettering society, despite “some of the antigovernment rants from certain quarters.” He enumerated the institute’s multiple contributions, commenting that along with the obvious scientific itinerary, the institute adds vibrancy to local and state economies.

“The NCI’s yearly budget is just a hair more than $5 billion, which is spent mainly on grants that support thousands of individual scientists, scientific teams, centers, and training programs. However, our budget has remained flat for the past 5 years, and when inflation is factored in, NCI’s purchasing power has decreased by about 20% over the past 9 years,” Dr. Varmus explained.

He continued, “Because of the discrepancy between the promise of science and adequate funding, the biomedical ecosystem is under unusual stress, putting the United States at risk of losing our global scientific leadership role.”

Three Categories of Good News

Dr. Varmus broke the NCI into its constituent parts, briefly explaining the goals of each sector. He then asked the rhetorical question: “How are we doing on the goal with which NCI was initially founded—conquering cancer?” In answer, he explicated the dizzying array of biologic complexities of cancer that have confounded faster progress. Then he transitioned into the more realistic goal of controlling and managing cancer, which set the stage for what he called “three major categories of good news.”

“First, we’ve seen a slow but steady decline in cancer mortality rates, roughly 1% to 2% per year over 2 decades, which is the best single measure of how we are doing in the battle against cancer. Second, this progress is not attributable to a single factor, but rather to a combined set of advances in early detection and preventive methods,” Dr. Varmus said.

“In addition, we’ve improved survival with a growing array of targeted therapies, the most dramatic of which is imatinib (Gleevec) for chronic myeloid leukemia. Moderate success has been achieved with targeted therapies in certain forms of lung cancer and myeloma. Moreover, novel research in immunotherapies shows promise in harnessing our body’s immune system to fight cancer,” Dr. Varmus said. He also mentioned advances in surgical and radiotherapy techniques, along with improvements over the past 2 decades in symptom management.

He then discussed the third category of “good news”—advances in the basic understanding of the underlying properties of the disease. “We now know unambiguously that cancer is a disease of our genomes in which the genetic information is either changed or damaged. And we have new diagnostic categories that are defined by these genetic changes, which give rise to what we now refer to as precision medicine,” Dr. Varmus said.

Scientific Dilemmas and Fiscal Constraints

Despite the advances, Dr. Varmus said the decrease in age-adjusted mortality in many cancers is unacceptably slow. “Moreover,” he continued, “several early detection methods have been overrated, most notably for prostate cancer. And although many cancers are behavior driven, we’ve had insufficient success in tobacco and weight control programs.”

Dr. Varmus used a single gene to highlight the scientific dilemma. “We have had significant scientific leads that simply haven’t materialized—like the KRAS mutation, which accounts for about 30% of all cancers—yet we still haven’t developed targeted therapies to address that clinical challenge.”

After restating the obvious problem of deciphering the complex, heterogeneous biology of cancer, Dr. Varmus affirmed that inadequate financing leads the list of impediments to cancer research. “Because of fiscal constraints, we currently only fund 14% of our grant applicants. Secondary fallout from this stringency is the chilling effect it has on young researchers, many of whom might shy away from the NCI because they feel the atmosphere is self-limiting,” Dr. Varmus said.

“[Underfunding] generates an aversion-to-risk attitude by grant applicants and review panels, and consequently, they support safe science instead of revolutionary science,” he said.

Further Impediments

“Researchers in the cancer community are also faced with an unprecedented wave of data, and we currently don’t know how to create clinical correlations from the different sets of data; solving that informatics problem is another huge challenge,” he noted.

Dr. Varmus also addressed a cultural impediment: “I have been a strong proponent of making scientific materials and literature open and accessible so investigators can freely exchange their reagents and findings. Open science is one way to partially counteract the stifling effect of fiscal stringency, so it’s an important goal,” he stressed.

“We are at an unprecedented time in our ability to turn our understanding of cancer into major clinical advances. Yet, it is a sobering time because medical research is hindered by financial shortfalls. Naturally, any cuts to our already tight budget would have devastating consequences to the NCI, an institute that contributes greatly to the public welfare. I remain an optimist, but we have to temper our goals,” Dr. Varmus concluded. n

Disclosure: Dr. Varmus reported no potential conflicts of interest.