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Proposed NiH Budget Falls Flat for 2013

After President Obama highlighted the importance of innovation and scientific advancement in his State of the Union Address in January, many in the biomedical research community hoped that funding for NIH might be on the rise. However, his proposed budget for fiscal year (FY) 2013, released in February, calls for holding NIH funding at its current level.

But given the troubled economic times, level funding might be considered a victory. The Office of Management and Budget had asked all departments and agencies last August to submit 2 budgets, with requests 5% and 10% below final 2011 appropriations.

“In a constrained fiscal environ-ment, when the budget for the Department [of Health and Human Services] as a whole is declining, NIH is maintained at the FY 2012 level of $30.9 billion, reflecting a priority for biomedical research as an investment that promises to deliver better health and drive economic growth,” says NIH Director Francis Collins, MD.

NIH aims to support 9,415 new and competing research project grants in FY 2013, 672 more than in FY 2012. To do so, inflationary al-lowances for competing and continu-ation grants would be discontinued and noncompeting continuation grants would be trimmed by 1%. (To put this in perspective, NIH estimated the rate of biomedical research inflation at 2.8% in 2011.) Moreover, awards totaling $1.5 mil-lion or more to any principal inves-tigator would receive “additional scrutiny and review.”

Like NIH overall, the National Cancer Institute is essentially level-budgeted at $5.1 billion.

One priority for NIH is the new National Center for Advancing Translational Sciences, described as “the nation’s hub for catalyzing innovations in translational science.” Its proposed $639 million budget is an 11% rise from FY 2012 funding.

Congress won’t rubberstamp the President’s proposals nor make final decisions on spending any time soon; Washington insiders don’t expect

to have a budget in place until after November’s presidential election. Until then, advocates will continue to press for additional research funding. Says Research!America President and CEO Mary Woolley, “Such things can happen even against what seem like very difficult odds.” ≠

what Patients Don’t Get About Phase i Trials

People enrolled in phase I clinical trials often equate medical research with medical care and misjudge the risks and potential benefits of partici-pating in a trial, according to a study by researchers at the Emory University School of Medicine in Atlanta, GA (Cancer published online 2012 Jan 31). Suggesting a need for more straight-forward consent forms, the study also “shows that the picture of understand-ing is much more complex than we thought,” says lead investigator and research ethics professor Rebecca D. Pentz, PhD.

Pentz and her team asked 95 patients in phase I clinical trials of cancer therapies 2 questions about the purpose of the trial: Is the re-search study mostly intending to help  research and gain knowledge or mostly intending to help you as a person, and does the research study or your physician decide the treatments?

Just 31 participants correctly answered both questions.

Participants were also asked why they enrolled in the study, what benefits they hoped to gain, what the study’s risks were, and whether any risks were of special concern. Additionally, they estimated their probable benefits and risks.

Nearly all—89 of 95—incorrectly estimated the risk and chance of benefit of joining a phase I trial, with 13 respondents asserting that there were no risks. Fifty-nine people estimated that they had at least a 70% chance of personal benefit. However, the investigators did not conclude that these misestimates demonstrated a high level of misunderstanding, because most participants explained that their estimates of benefit were not intended to be statements of fact, but rather what they hoped would happen.

Frank McCormick, PhD, director of the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center,

was inaugurated as president of the American Association for Cancer Research (AACR) in April at the organization’s 103rd annual meeting in Chicago. He will serve a 1-year term, succeeding Judy E. Garber, MD, MPH.

McCormick holds the E. Dixon Heise Distinguished Professorship in Oncology and the David A. Wood Distinguished Professorship of Tumor Biology and Cancer Research at UCSF. In addition, he is the associate dean of the UCSF School of Medicine.

Also at the or-ganization’s annual meeting, Beatrice Mintz, PhD, received the annual AACR Award for Lifetime Achievement in Cancer Research,

honoring the lasting impact of her research and commitment to progress against cancer.

Mintz, the Professor and Jack Schultz Chair in Basic Science at the Fox Chase Cancer Center in Philadelphia, pioneered the notion of a chimeric, or transgenic, mouse. She was also the first to suggest and prove the importance of a tumor cell’s environment in its cellular identity and function.

John Mendelsohn, MD, who served as president of The University of Texas MD Anderson Cancer Center from 1996 to 2011, received the annual AACR

Margaret Foti Award for Leadership and Extraordinary Achievements in Cancer Research at the organization’s annual meeting. The award recognizes his sustained leadership and achieve-ments in cancer research. Mendelsohn’s pioneering work helped establish the field of targeted therapy, specifically EGFR tyrosine kinase inhibition.

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on the other. The locks are based on aptamers, sequences of DNA that bind tightly and specifically to particular mol-ecules—for instance, cell-surface proteins typical of T cells or aggressive leukemia cells. When the aptamer locks find their targets, they latch on, and the DNA box springs open, revealing the payload. The nanorobot’s 2 aptamers can target different antigens.

In the experiments with leukemia cells, the researchers loaded the DNA nanorobots with an antibody drug that binds to a surface receptor on the cancer cells, initiating a signaling cas-cade that flips the cells’ kill switch. The study suggested that the nanorobots didn’t interact with other types of cells.

The researchers call the DNA drug carrier a nanorobot because it performs a logic function—adding 2 input signals (the presence of the 2 molecular keys) to generate an out-put (opening to reveal its payload) like an “AND” logic gate in electronics.

Shawn Douglas, PhD, a fellow at the Wyss Institute for Biologically Inspired Engineering at Harvard and co-first author on the Science paper, notes that before the researchers can test the DNA nanorobots in mice, they must scale up production a thousand-fold. He adds that they’ll have to modify the DNA structures so that the structures will stay in the circulation—it’s likely the current design would be cleared from the bloodstream quite rapidly. ≠

Participants almost never listed the risks from the extra procedures that are part of research—blood draws every half hour, for example. “They just didn’t focus on what is unique to research,” explains Pentz. “Physicians have to hammer home that research isn’t just me taking care of you.”

But the most surprising finding, Pentz says, was the significant number of patients who estimated their per-sonal benefit as lower or their personal risk as higher than that of the rest of the population. “I did not anticipate that,” she adds. “The phase I picture is psychologically complex.”

Although current consent forms explain how a clinical trial will differ from standard care, the details are gener-ally woven throughout the document. Clinical trial subjects might have a better understanding of the trial’s intent, as well as the risks and potential benefits of participating, if the information was presented in a tear-out chart, says Pentz. Her team’s next study will assess the ef-fectiveness of just such a form. ≠

DNA Nanorobot signals Cancer Cells to Die

A drug prototype based on a barrel of DNA stuffed with antibodies potentially could lead to cancer drugs that cause fewer side effects. The drug carrier can target particular cell types very specifi-cally, attach to their surface, and trigger signaling cascades within. Researchers at Harvard who developed the DNA nanorobot have demonstrated a variety of capabilities, including the ability to trigger apoptosis in leukemia cells in vitro (Science 2012;335:831–4).

The DNA nanorobot was designed by researchers led by George Church, PhD, professor of genetics at Harvard Medical School, using a method called DNA ori-gami. Over the past several years, research-ers have developed software programs that write sequences of DNA strands that, when synthesized and mixed together, will self-assemble to form complex 3- dimensional shapes such as boxes.

The Harvard group built on this work, designing a DNA cylinder lined with protein-binding sections on the inside that can hold onto a payload. The cylinder opens up like a clamshell, with DNA springs on one side and DNA locks

•  A mouse reference library called the Collaborative Cross (CC) provides data on genetic variation contained in hundreds of specially bred mice. Researchers said that the publicly available CC mice have much more genetic variation than normal lab mice, and thus more closely mirror the genetic complexity found in humans (G3 2012;2:153–6).

•  Oxford Nanopore Technologies has presented DNA sequence data using its nanopore “strand-sequencing” system, which is said to deliver ultra-long-read-length single-molecule sequence data with real-time results and competitive accuracy. The Oxford, UK–based company says that next year a high-end version of its scalable systems will be able to deliver a complete human genome in 15 minutes.

•  Duke Cancer Institute celebrated the opening of the new Duke Cancer Center in February. The 7-story, 267,000-square-foot structure, designed to fully integrate cancer care and re-search, will include dedicated spaces where patients can speak with research nurses about available clinical trials.

•  Dainippon sumitomo Pharma of Osaka, Japan will buy Boston Biomedical inc. (BBI) of Norwood, MA, for $200 million, plus development milestones up to $540 million and commercial milestones up to $1.89 billion. BBI’s BBI608 and BBI503 oral compounds may become the first drugs in the world targeting cancer stem cells.

•  NIH’s National Center for Biotechnology Information has unveiled the Genetic Testing Registry, which collects vol-untary submissions of genetic test information by providers.

•  A study by Italian and Swiss researchers estimates that 1.3 million people in the european Union (eU) will die from cancer in 2012. That figure would consti-tute a drop in the rate of cancer deaths of 10% in men and 7% in women com-pared with 2007 statistics (Ann Oncol published online 2012 Feb 28).

•  Despite FDA actions, cancer drug shortages “will remain for the fore-seeable future,” says Jack Muckstadt, professor of engineering at Cornell University and the former director of Cornell’s School of Operations Research and Industrial Engineering. “Simply put, there are no financial in-centives for increasing capacity within or between manufacturers.”

Noted

For more news on cancer research, visit Cancer Discovery online at http://CDnews.aacrjournals.org.

A DNA nanorobot springs open like a clamshell to reveal its payload, antibody drugs (purple). The DNA shell is held together by 2 DNA locks (red) that open when they meet molecular keys (green) found on the surface of a cell. Top left shows a side view of the DNA shell in its closed state.

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Cancer Research. on February 13, 2021. © 2012 American Association forcancerdiscovery.aacrjournals.org Downloaded from

Published OnlineFirst February 23, 2012; DOI: 10.1158/2159-8290.CD-ND2012-011