American Association for Cancer Research Annual Meeting

American Association for Cancer Research Annual Meeting

Source:

Sharpless NE. NCI director’s address. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting): April 10-15, 2021.

Disclosures: Sharpless reports no relevant financial disclosures.
April 12, 2021
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‘Concerted effort’ needed to reduce cancer mortality by 4% annually, NCI director says

Source:

Sharpless NE. NCI director’s address. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting): April 10-15, 2021.

Disclosures: Sharpless reports no relevant financial disclosures.
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Reducing the cancer mortality rate by 4% per year through 2026 would cut the rate to half of its all-time peak, NCI Director Norman E. “Ned” Sharpless, MD, told attendees of the virtual American Association for Cancer Research Annual Meeting.

The rate of decline in cancer mortality has accelerated over the past decade, reaching 2.4% in 2018, the last year for which data are available, Sharpless said. However, he said maintaining that rate of decline wouldn’t halve the highest cancer mortality rate — which peaked at 215 deaths per 100,000 people in the early 1990s — until 2040.

Effect of annual reduction in cancer mortality on halving peak rates
Data were derived from Sharpless NE. NCI director’s address. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting): April 10-15, 2021.

“[A 4%] reduction would represent a huge advantage, a symbol toward ‘ending cancer as we know it,’” Sharpless said, referring to a goal of President Joe Biden’s agenda. “How do we bridge that distance between what we’ve been able to achieve and where we want to go? This will not be through one smashing breakthrough, one big discovery or one major initiative. There will be no silver bullets here.

Norman E. “Ned” Sharpless

“Instead, we need a concerted effort with lots of complex parts coming together to build that bridge — this bridge from toxic and marginal therapies and modalities from the past to new approaches of the future,” Sharpless added. “We need a bridge from places where the long-term responses, even cures, go from being uncommon to being the expectation. And we need a bridge from the important gains in prevention through things like tobacco control to effective approaches for all the main drivers of cancer risk. Perhaps, and most importantly, we need a bridge from the visionary researchers of the past whose science led to the breakthroughs and progress of the recent decades to the enterprising young investigators whose work today will lead these future advances.”

The path forward to building this bridge “is not obvious,” Sharpless said, but will rely on federal funding and new collaborative initiatives, more emphasis on government-sponsored trial participation, research into multicancer early detection tests and drug targets, and intensive efforts to address health equity.

Support in Washington

The Biden administration has emphasized making progress against cancer as a top priority and, on Friday, released the president’s budget for fiscal year 2022 that would greatly increase federal funding for cancer research.

Although this high-level outline of the president’s budgetary priorities may not reflect what ultimately passes in Congress, it reflects the strong public and bipartisan support for cancer research, Sharpless said.

Two components of that budget are particularly important for cancer research, Sharpless said, including the suggested total funding increase to the NIH of $9 billion, which would include $2.5 billion for the institutes of the NIH, the largest of which is the NCI.

“An increase of this size would translate into a substantial increase in the NCI’s base budget for 2022,” he said. “Over the last several years, the NCI has had steady increases, on the order of $100 million to $200 million but, at that level, 2022 would likely be a much larger increase if the president’s budget were taken up as is.

“This would be key to allowing the NCI to continue to increase paylines and success rates for grant applications,” Sharpless said, adding that increasing grant paylines to the 15th percentile by 2025 for established investigator R01s — which are currently at the 11th percentile, up from a nadir of the eighth percentile — has been one of his top priorities.

“The type of support proposed in the president’s budget would allow NCI to invest robustly in investigator-initiated science, which I believe is how we make progress for our patients, because it’s the basic translational discoveries that really move the needle,” Sharpless said.

In addition, the president’s budget proposes $6.5 billion to fund a new national effort called the Advanced Research Projects Agency-Health, or ARPA-H, modeled on the military’s Defense Advanced Research Projects Agency, or DARPA. This new NIH-housed effort would be focused on advances in research for cancer and other diseases, according to Sharpless.

To achieve Biden’s goal of “ending cancer as we know it,” it’s important to define what that means, Sharpless said.

“My view is that, given the fundamental links between cancer and aging, I think a world that is totally free of cancer death is an unrealistic goal anytime soon,” he said. “The president didn’t say that we should eradicate all cancer, but that we should end the tragedy of cancer. When I think about the tragedy of cancer, I think of ... the consummate unfairness of cancer. I don’t expect to end all cancer deaths, but I think eradicating a vast majority cancer, especially in young and otherwise healthy people, is doable.”

Directions of promise

Sharpless outlined several directions of promise that will be key in addition to investing in investigator-initiated research to achieve the 4% yearly decline in cancer mortality.

One idea is to use ARPA-H to build a large national trial of multicancer early detection tests, or blood-based screening tests to find early cancer in healthy adults, that could start as early as 2022, he said.

“Such screening tests have to be evaluated with the appropriate power and endpoints to determine if any of these new technologies that are being advanced for this purpose can really reduce mortality at the population level,” Sharpless said. “These technologies undoubtedly hold immense progress, but cancer screening is tricky. We all are very familiar of the problems of overdiagnosis and overtreatment, so we have to get this right.”

Another idea Sharpless proposed is to devote significant resources to government-sponsored clinical trials. NCI enrolled about 30,000 patients onto trials in 2020, a figure that could be doubled, Sharpless said, by expanding trials to community practices, focusing on underserved populations, loosening eligibility criteria and improving patient matching to trials.

“The idea in expanding clinical trials is not to compete with industry for patients, but to do the sorts of trials that the NCI takes on that are vitally important because they are the types of trials that industry won’t do or can’t do — things like prevention trials, de-escalation trials and complex multimodality trials, and trials using a novel adaptive design with regulatory endpoints constructed in mind,” he said. “There are plenty of patients who are not enrolling on any trial right now, and reinvigorating trials with the kinds of capabilities that ARPA-H would provide is a tremendous opportunity to accelerate progress.”

Lastly, Sharpless proposed a new commitment to advancing drug development through accelerated approaches to structural biology and medicinal chemistry.

“The idea here is for the NCI to lead a large effort to identify protein structure using technologies like cryo-electron microscopy while also developing new analytics for drug discovery, like machine-learning approaches to predict protein folding and small-molecule binding, or like molecular dynamic simulations to identify dynamic binding pockets in a protein and really find opportunities for heretofore undruggable cancer targets,” he said. “Marry all of these approaches with novel ways to make these small-molecule drugs and biologics, and we could create a national network of GMP foundries for novel cellular therapeutics. We could really explore the entire range of therapeutic approaches on different molecular targets using this whole range of technologies.”

Underlying all these efforts must be intensive efforts to address health equity, Sharpless said.

“The president did not say he wanted to end cancer as we know it for some people,” he said. “The goal is to make this progress for all people, regardless of race, ethnicity, wealth or access. The COVID-19 pandemic as put a bright spotlight on the disparities and inequities in American health care.”

Oncologists are familiar with these problems, as cancer progress has long been hampered by health disparities, Sharpless added.

“We’ve known for some time that taking on health inequities and disparities will be a critical part of ending cancer as we know it,” he said. “But, that means more than just doing what we’ve been doing ... that means baking health equity into everything we do. It means addressing systemic racism and all the structural barriers that block our progress. We can’t leave huge portions of society behind and expect to make meaningful progress against cancer.”