Sharpless, 55, said in an interview that he has “tremendously mixed feelings” about leaving, because he has enjoyed his positions at NCI and FDA. But he said his time as a top federal health official has been “pretty tumultuous,” mostly because of the gratifying but exhausting work sparked by the coronavirus pandemic, including NCI’s role in helping evaluate coronavirus tests.

“My time in government,” Sharpless said, “should be measured in dog years.”

A longtime researcher who delved into the relationship between cancer and aging, Sharpless was director of the Lineberger Comprehensive Cancer Center at the University of North Carolina before joining NCI in October 2017.

He said he wanted to return to Chapel Hill to spend more time with his wife, an endocrinologist, and other family members, including his 89-year-old mother. He said he was not going to another job but expected at some point to return to academia.

As the nation’s top cancer doctor, Sharpless has been upbeat about progress against the disease, and has praised President Biden’s relaunched “moonshot” against cancer, which aims to cut the nation’s cancer mortality rate in half over 25 years.

“Making cancer less lethal and a more manageable disease, that is doable,” he said, adding he believes deaths can be significantly reduced, especially among young and otherwise healthy people. But to make such strides, he has said, the nation needs widespread improvements in clinical trials, increased aggregating and sharing of data, and stepped-up prevention and screening.

Sharpless has warned repeatedly about the deleterious effects of the pandemic, noting that millions of people missed routine cancer screening tests or delayed getting treatment. NCI modeling suggests an additional 5,000 to 10,000 people could die of breast cancer during the next decade because of pandemic-related delayed diagnoses and worse prognoses, he said, urging adults to resume screenings.

Cancer death rates have decreased significantly since 1990, in large part because of a sharp reduction in smoking but also because of new treatments, including immunotherapies that help the immune system “see” and fight cancer. Even so, about 1.9 million new cases of cancer and more than 609,000 cancer deaths are expected in the United States this year, according to the American Cancer Society.

That continuing toll has prompted some critics to argue that the nation needs new strategies to defeat cancer that focus less on finding breakthroughs and more on increasing prevention, improving quality of care and reducing the toxic effects of treatments. Cary P. Gross, professor of medicine at the Yale School of Medicine, wrote in the Hill newspaper that governments should take further steps to reduce smoking and increase vaccination for the human papillomavirus, which causes cervical and other cancers.

The NCI director’s departure comes as the Biden administration grapples with a highly uncertain future dominated by a pandemic that may be easing — or may be in a temporary lull. The efforts are complicated by a raft of recent personnel changes.

In December, Francis Collins stepped down as director of the National Institutes of Health after 12 years. In February, Eric Lander, Biden’s top science adviser, whose office is taking the lead on the reboot of the cancer moonshot, resigned after admitting to “disrespectful and demeaning” treatment of underlings. Collins recently took a temporary post as Biden’s chief science adviser.

White House coronavirus response coordinator Jeff Zients is leaving his job this month and will be replaced by epidemiologist Ashish Jha, dean of the Brown University School of Public Health.

In another development on cancer research, Congress recently funded a new Advanced Research Projects Agency for Health, a priority for Biden. The new agency will attempt to accelerate progress on serious illnesses, including cancer, Alzheimer’s and heart disease.

Among cancer specialists and patients, the new agency generates mixed views. Some worry ARPA-H, as it is known, will siphon funding from the cancer institute, while others say it will be nimbler than NCI in tackling high-risk research. Biden’s budget proposal for the next fiscal year asked for a small reduction in NCI funding and billions for the new agency.

Sharpless said the moves around the new agency did not affect his decision to leave and that he believes ARPA-H could be useful if given flexibility on contracting, personnel and other rules that sometimes slow down government bureaucracies, and if it coordinates with the cancer institute.

After leading the cancer institute for a year and a half, Sharpless moved to the FDA in April 2019 as acting head after Scott Gottlieb resigned as commissioner. After the Trump administration nominated MD Anderson Cancer Center official Stephen Hahn to be FDA commissioner, Sharpless returned to the NCI directorship.

“Ned had a profound impact across two agencies, over a period when the treatment of cancer underwent major advances and we confronted a generational pandemic,” Gottlieb said. He credited Sharpless for NCI’s role in helping validate diagnostic tests for the coronavirus and for shaping how researchers “embraced the new field of immunotherapies.”

Sharpless said he is proudest of his efforts on pediatric cancer, including securing an extra $50 million a year over a decade to ramp up research.

“My thinking here evolved,” he said.

“I am an adult oncologist and I kind of thought this was a condition where American progress was satisfactory,” he said, referring to childhood cancer.

But his views changed and now he believes better treatments are urgently needed. While cancer is rare in children, patients often develop medical problems later in life, including second malignancies, from the toxic treatments, he noted.

NCI’s pediatric cancer initiative focuses on sharing data among children’s hospitals, clinics and networks to try to accelerate ways to improve care for children.

Sharpless also pressed to increase grants for investigators, who have faced intense competition in the past decade. He said increasing the share of applications that NCI can fund is a slow but ongoing process. Sharpless also created NCI’s Equity and Inclusion Program to develop a more diverse cancer workforce and to decrease health disparities.

Health and Human Services Secretary Xavier Becerra, in a statement, praised Sharpless’s work on the pandemic response and his efforts “to minimize the negative effects of the pandemic on people with cancer.”

Sharpless’s last day as NCI director is April 29. Douglas R. Lowy, principal deputy director at NCI, will serve as acting director.

“I think he was a great director, a serious scientist” who understood patients’ needs and the responsibilities of being NCI director, said Ellen V. Sigal, founder and chair of the Friends of Cancer Research, a nonprofit advocacy group.