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NCI Director Sharpless Outlines Ideas to Aggressively Lower Cancer Deaths

NEW YORK – In working toward President Joe Biden's goal of accelerating cancer research and reducing deaths from the disease, the National Cancer Institute should focus on improving blood-based early screening, expanding clinical trial access in the community setting, and developing advanced treatments, NCI Director Norman Sharpless said in an address at the American Association for Cancer Research annual meeting on Sunday.

In a speech in February, President Biden said that after the COVID-19 pandemic has been reined in, he wanted his administration to put their energies toward "ending cancer as we know it." More recently, on Friday, the White House released the president's discretionary budget request, in which Biden proposed $51 billion in funding for the National Institutes of Health for FY2022. An increase of $9 billion to the NIH budget would also mean a substantial increase in the NCI's base budget for 2022 compared to past years.  

Moreover, the president asked Congress for $6.5 billion to launch a new NIH center, called the Advanced Research Projects Agency for Health (ARPA-H), which will focus on accelerating research into cancer and other diseases. At the AACR annual meeting, Sharpless discussed how he hoped to use additional funding, should Congress approve it, to achieve the president's stated goal of "ending cancer as we know it."

Sharpless explained foremost that it is unrealistic to expect that all cancer will be eradicated any time soon, but he proposed several strategies that could quickly reduce cancer mortality over the next five years. "I don't expect to end all cancer deaths," he said. "But I think eradicating a vast majority of cancer, especially in otherwise young and healthy people … is doable."

However, Sharpless wanted to place some hard metrics by which to measure success in this regard and said that the goal should be to try to cut age-adjusted cancer mortality by half from its peak in the early 1990s. Back then, 215 deaths per 100,000 were due to cancer. Currently, 150 deaths per 100,000 are due to cancer, a 30 percent decline from the 1990s. However, the rate of decline over the past three decades has been too slow, in Sharpless's view, and he would like the government and cancer research community to get behind the goal of reducing cancer mortality by 50 percent by 2026 from its peak in the 1990s, which would require an average of 4 percent reduction in cancer deaths over the next five years.

"This would be the sort of clear and indisputable result we'd have to see on our way to ending cancer as we know it," he said, noting that such aggressive reductions in mortality would require private-public collaborations to marshal all the recent advances the field has made in cancer prevention, screening, and advanced treatments.

"Based on what we know about cancer today, this will not be [achieved] through one smashing breakthrough or a big discovery or one major initiative. There will be no silver bullets here," he said. "Instead, we need a concerted effort, with lots of complex parts, coming together to build that bridge … from toxic and marginal modalities of the past to these new approaches of the future."

Toward this end, he proposed three ideas that he hoped Biden's proposed new agency, ARPA-H, could assist with. First, the NCI is considering doing a large national trial, or a series of trials, of multi-cancer early detection blood tests, which aim to detect cancers in otherwise healthy adults. The first of these trials may start as soon as next year, Sharpless predicted.

"Such screening tests have to be evaluated with the appropriate power and endpoints to determine if any of these new technologies … can really reduce mortality at the population level," Sharpless said, cautioning that cancer screening is tricky. "We all are very familiar with the problems of overdiagnosis and overtreatment, so we really have to get this right."

Second, he proposed the NCI should commit significantly more resources to government-sponsored clinical trials. The institute enrolled around 30,000 patients into clinical trials last year, but Sharpless is optimistic the NCI can double that number by expanding enrollment into the community setting, particularly underserved populations, where participation has been historically low. "We'd have to expand [eligibility] criteria for patients … and we'd have to take on new ways to enhance patient matching to really connect patients to the right trial," he said.

Third, Sharpless proposed bolstering NCI's drug discovery efforts toward improving understanding of structural biology and medicinal chemistry. Within such a program, researchers would focus on identifying protein structure, using technologies like cryogenic electron microscopy, and employ advanced analytic approaches, such as machine learning to predict protein folding and small molecule binding, and simulations to identify dynamic binding pockets for therapies that inhibit previously "undruggable targets."

The NCI could find novel ways of making these drugs and "create a national network of [good manufacturing practices] foundries for novel cellular therapeutics, such as CAR T cells and NK cells and beyond," Sharpless said. "We can really explore the entire range of therapeutic approaches [against] different molecular targets using [these] … technologies."

Ultimately, all of NCI's efforts to eradicate cancer will have an overarching focus on advancing health equity, especially after the COVID-19 pandemic has laid bare the vast healthcare disparities in the US. According to Sharpless, the NCI will be advancing new efforts to "bake health equity into everything we do," in order to address systemic racism and structural barriers.  

"The president did not say he wanted to end cancer as we know it for some people," Sharpless said. "The goal is to make this progress for all people, regardless of race, ethnicity, wealth, or access."  

The president's budget is merely a proposal and it is ultimately up to Congress to decide whether to increase funding for life sciences research. Sharpless noted that in 2017, his first year at the NCI, then President Donald Trump requested a 26 percent cut to the NCI's base budget. Those reductions didn't materialize ultimately because cancer research has bipartisan support in Congress, and Sharpless remained optimistic that this will continue to be the case.

Moreover, how the activities of ARPA-H will "fit with ongoing efforts at the NCI" hasn't yet been ironed out. "But having ARPA-H as part of the NIH is really good news for the NCI," Sharpless said.

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