1. Rosenthal, Eric T.

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Barry Kramer's official return to the National Cancer Institute last month brought him back to the future of cancer prevention, which will have a decidedly collaborative and molecular direction.


When I reported last summer (8/1/11 blog post) that NCI Director Harold Varmus, MD, had announced the appointment of Barnett S. Kramer, MD, MPH, as the next director of the Division of Cancer Prevention, Varmus said "not all the paperwork has been signed as yet, but I'm taking the risk of saying that it will be signed."


That risk paid off and now, some three months later after going through the lengthy committee approval process for senior officials, Kramer cut short his short-lived retirement from government service to take the top NCI leadership post in cancer prevention.


During his first week on the job, Kramer told me that Varmus had asked him last spring for advice about the future of prevention.


"Harold was in the process of recruiting a director of the prevention division and [although not a candidate at the time] I went over my ideas about what I thought should be the direction of cancer prevention-including understanding molecular pathways and the microbiome [which NIH is studying through its Human Microbiome Project]-when he asked me if I'd consider the position."


Several months earlier Kramer had retired after nearly a decade as the National Institutes of Health Associate Director of Disease Prevention and Director of NIH's Office of Disease Prevention to focus on his other roles as Editor-in-Chief of the Journal of the National Cancer Institute (JNCI) (published by Oxford University Press and not affiliated with NCI as of about 10 years ago) and Chairman of NCI's Physician Data Query (PDQ) Screening and Prevention Editorial Board and as a member of PDQ's Treatment Editorial Board.


In July he will step down as JNCI Editor-in-Chief after more than 18 years in the position. (Disclosure: I write occasionally for JNCI's news section.)

BARNETT S. KRAMER, M... - Click to enlarge in new windowBARNETT S. KRAMER, MD, MPH, Director, Division of Cancer Prevention, National Cancer Institute.

Kramer said he had served for more than 30 years with the federal government and wanted to spend more time conducting literature searches and writing and editing for PDQ, as well as increasing his skills in evidence-based decision-making, but Varmus's offer was also very central to his interest in cancer prevention and screening.


Prior to joining NIH Kramer had been NCI Deputy Director of Cancer Prevention, serving under Peter Greenwald, MD, DrPH, who was named Associate Director for Prevention in the Office of the NCI Director earlier this year.


Although Kramer's former position had not been filled since he left, Lori Minasian, MD, who had been acting cancer prevention director until Kramer's appointment, has now assumed the role of acting Deputy Director in addition to her regular job as Chief of the Community Oncology and Prevention Trials Research Group.


Wants to Bring 'Strongest Evidence Possible'

Kramer said that he wants to bring the strongest evidence possible to screening and prevention, and plans to expand into molecular approaches that would help better identify which cancers need to be treated versus those that are more indolent.


He also wants to expand collaboration through NCI's various divisions as well as with other NIH institutes and beyond, and plans to hire someone to look into collaborations that could help provide new leads for cancer prevention.


"At its core, prevention is developing interventions to block or delay progression of cancer for people who don't have cancer, and an understanding of molecular pathways will afford additional insights as well as additional opportunities to target those pathways for prevention and screening."


Screening has long been a key interest of Kramer, who said that earlier in his career he realized clinical approaches were very different from public health and that he needed more education to learn more about the science of the denominator for a fuller appreciation of where cancer therapy fit within the spectrum of public health. He worked on his MPH at Johns Hopkins when he was at NCI in the early 1990s.


Screening sits at the interface between medicine and public health, because it is often applied in a clinical setting but involves large numbers of people, many of whom are generally healthy, he said.


While at NIH he helped organize its annual Medicine in the Media workshop so journalists would have the tools to convey medical and scientific evidence in context and be able to evaluate studies more independently, which he saw as another aspect of public health.


"There is an element of over-diagnosis associated with many screening tests that begin to pick up slower growing or non-progressive cancers, with prostate cancer as the poster case," he said.


"We need to understand the natural history of tumors and look at their molecular pathways to get insight into a population of cancers that can be treated differently or not treated and observed, and we also need to look at the interval cancers that are missed by screening and tend to grow very quickly."


He said that comparing the molecular fingerprints of screening-detected cancers with those that are interval cancers can help provide insights into which may or may not need to be treated when they are detected, and can also serve as molecular targets for prevention.


Screening, he explained, is usually aimed at people with cancer or premalignant lesions who are not symptomatic, and prevention is aimed at those who don't have cancer or at averting any progression to cancer.


There is some overlap, though, of course, with cervical cancer a classic example of using a screening technique aimed at primarily preventing an actual invasive cancer by picking up pre-invasive lesions, he said.


Kramer also stressed the importance of expanding molecular understanding not just of tumors but also their surrounding normal tissue as well, and said his division would be getting involved in studying the microbiome-microbiological organisms such as bacteria and viruses humans carry that participate in our overall health-including their role in energy exchange and obesity and its relation to cancer.


Disease Prevention Beyond Cancer

His time at NIH also provided him with a view of disease prevention beyond cancer, and he said he wants to look "in a meticulous way at trials done in humans to manage, treat, or prevent other non-cancerous diseases to see if there are any signals of cancer prevention," noting that there is "a hint" that the diabetes drug metformin might lower the risk for some cancers.