National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
February 10, 2009 • Volume 6 / Number 3

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NEWS

On February 4, President Obama signed an expansion of the State Children's Health Insurance Program, which included a federal tax increase on cigarettes, 'little cigars,' and cigarillos. Photo by Win McNamee

Health Groups Hail Increase in Federal Tobacco Taxes

Taxes on cigarettes, “little cigars,” and cigarillos will increase significantly under legislation signed by President Barack Obama on February 4. Funds from the increased tax on tobacco products will be used to offset the cost of the State Children’s Health Insurance Program (SCHIP) expansion. Data show that youth are more responsive to cigarette price increases than adults. Both the expansion of SCHIP and the tax hike were applauded by numerous medical, health care, and tobacco control organizations. Read more > >

COMMENTARY

Director's Update: Budget Proposal Highlights Progress and Opportunities in Cancer Research

Cover art for The Nation's Investment in Cancer Research Last week NCI released The Nation's Investment in Cancer Research, an annual report intended to directly inform the President about the progress and opportunities in our continuing efforts against cancer and to justify the administration’s budget request to Congress for an additional $2.1 billion to fund the Nation’s battle against cancer. At a time of great economic challenge, the 2010 report demonstrates how NCI’s deep commitment to outstanding science benefits all Americans.  Read more > >

A Conversation With...Dr. Joe Harford

The director of NCI’s Office of International Affairs discusses the history of the Middle East Cancer Consortium, its recent efforts, and the impact of health diplomacy in the region.  Read more > >

IN DEPTH

UPDATES

  • Cancer.gov Update

    • New Dietary Data Available Online
    • NHANES Dietary Web Tutorial Guides Data Users
  • Notes

    • NCI Lecture Series Features Dr. Napoleone Ferrara
    • Bridge Awards Available from SBIR
    • NCAB Convenes Its First Meeting of 2009

The NCI Cancer Bulletin is produced by the National Cancer Institute (NCI), which was established in 1937. Through basic, clinical, and population-based biomedical research and training, NCI conducts and supports research that will lead to a future in which we can identify the environmental and genetic causes of cancer, prevent cancer before it starts, identify cancers that do develop at the earliest stage, eliminate cancers through innovative treatment interventions, and biologically control those cancers that we cannot eliminate so they become manageable, chronic diseases.

For more information about cancer, call 1-800-4-CANCER or visit http://www.cancer.gov.

NCI Cancer Bulletin staff can be reached at ncicancerbulletin@mail.nih.gov.

Featured Article

Health Groups Hail Increase in Federal Tobacco Taxes

On February 4, President Obama signed an expansion of the State Children's Health Insurance Program, which included a federal tax increase on cigarettes, 'little cigars,' and cigarillos. Photo by Win McNamee. On February 4, President Obama signed an expansion of the State Children's Health Insurance Program, which included a federal tax increase on cigarettes, "little cigars," and cigarillos. Photo by Win McNamee.

Taxes on cigarettes, “little cigars,” and cigarillos will increase significantly under legislation signed by President Barack Obama on February 4.

The legislation’s chief focus is the expansion of the State Children’s Health Insurance Program (SCHIP), which provides health insurance coverage for children whose families do not qualify for Medicaid and who do not have insurance through an employer or the resources for private insurance. Funds from the increased tax on tobacco products will be used to offset the cost of the SCHIP expansion.

The last federal excise tax was passed in 1997 and went into effect in two stages—$0.10 in January 2000 and $0.05 in January 2002, raising the tax to a total of $0.39. Under the new law, federal taxes on packs of cigarettes will increase by $0.62, while the tax on little cigars will increase by $1.01 and on cigarillos by $0.35. For little cigars—similar in size to cigarettes, but wrapped in a tobacco leaf—the increase brings their tax in line with cigarette taxes. The tax on cigarillos, which are thinner versions of traditional cigars, was raised from $0.05 to $0.40.

Both the expansion of SCHIP and the tax hike were applauded by numerous medical, health care, and tobacco control organizations, including the American Cancer Society, American Lung Association, American Medical Association, and Campaign for Tobacco-Free Kids (CTFK).

“Increasing the federal tobacco tax to fund SCHIP is a win-win proposal that will help children get the health care they need, while also acting as a deterrent to young smokers and potential smokers,” said American Medical Association President Dr. Nancy Nielsen.

Data show that youth are more responsive to cigarette price increases than adults, with a 10 percent increase in the price of cigarettes estimated to reduce youth smoking by almost 7 percent compared with 2 percent among adults.

“The passage of this legislation means that little cigars and cigarillos will be taxed at the same rate as cigarettes. Increasing the price of these tobacco products will help make them less appealing to youth,” said Dr. Cathy Backinger, chief of NCI’s Tobacco Control Research Branch.

Declines in cigarette smoking among youth have stalled in the past 4 years, Dr. Backinger explained, with 20 percent of youth reporting that they were current smokers in 2007. Data also show that youth are increasing their use of other tobacco products, including little cigars and cigarillos.

On the same day President Obama signed the SCHIP legislation into law, the American Legacy Foundation issued a news release with new findings showing that cigarillo use increased by 240 percent and little cigar use increased by 150 percent between 1997 and 2007.

Young African Americans appear to be the heaviest users of these products. Available evidence suggests that they favor one brand in particular, Black & Milds, often just called “Blacks.” In 2007, the Altria Group, which includes Philip Morris, acquired John Middleton, Inc., which manufactures Black & Milds.

According to the CTFK, the tobacco tax increases will prevent 2 million children from ever starting to smoke, help more than 1 million adult smokers quit, prevent nearly 900,000 smoking-related deaths, and generate more than $44 billion in health care savings over the long term.

Cancer Research Highlights

Combining Targeted Drugs Is Worse in Colorectal Cancer

A randomized clinical trial testing chemotherapy combined with bevacizumab (Avastin) and cetuximab (Erbitux), and comparing this with chemotherapy and bevacizumab alone, found that the addition of cetuximab actually shortened patients’ recurrence-free and median survival. This runs counter to some studies using animal models of cancer, which suggest that combining a drug that targets vascular endothelial growth factor (VEGF) with a drug that targets epidermal growth factor receptor (EGFR) may be more effective than either drug alone. The trial results appeared February 5 in the New England Journal of Medicine.

Investigators from the Netherlands enrolled 755 patients with metastatic, inoperable colon or rectal cancer into the trial, continuing treatment until disease progression, death, or unacceptable side effects. Overall, “the addition of cetuximab significantly decreased the median progression-free survival” from 10.7 months to 9.4 months, they reported. Median overall survival was 20.3 months for patients receiving chemotherapy and bevacizumab and 19.4 months for patients receiving chemotherapy, bevacizumab, and cetuximab. Patients who received cetuximab reported less improvement in overall quality of life and health during treatment.

The researchers analyzed these results in the context of whether patients had tumors with the normal or mutated form of a gene called KRAS. Numerous studies have shown that only patients with normal KRAS genes benefit from drugs that target EGFR, including cetuximab. Patients with mutant KRAS who were given cetuximab had a significantly shorter progression-free survival than patients in the chemotherapy and bevacizumab arm; for patients with normal KRAS, cetuximab had no effect on progression-free survival.

The cause of these unexpected negative results are not clear, explained the authors, though a negative interaction between cetuximab and bevacizumab is one possibility.

Preserving Ovaries May Be Safe for Some Endometrial Cancer Patients

Because estrogen may fuel its spread, removing the uterus (hysterectomy) and the estrogen-producing ovaries (oophorectomy) is the standard of care for endometrial cancer. However, data from a retrospective study published online January 26 in the Journal of Clinical Oncology suggest that for premenopausal women with early stage, low-grade endometrial cancer, removing the ovaries may not actually improve survival.

Dr. Jason D. Wright and colleagues from the Columbia University College of Physicians and Surgeons used the SEER database to compare the survival of 2,867 endometrial cancer patients who underwent oophorectomy with that of 402 endometrial cancer patients whose ovaries were preserved. All of the women were diagnosed between 1988 and 2004 and had hysterectomies.

Women whose ovaries were preserved were younger, more likely to have low-grade and early stage tumors, and were also less likely to receive adjuvant radiation than women who underwent oophorectomy. There was no impact on disease-specific, 5-year, or overall survival, even after controlling for these differences. When the researchers excluded those women who received pelvic radiation, which could have affected ovarian function, there was still no survival advantage to oophorectomy.

Oophorectomy induces early menopause; thus, leaving the ovaries intact could spare these women hot flashes, vaginal dryness, and long-term health implications, including increased risk of heart disease, osteoporosis, and hip fractures. “Given the potential consequences of surgical menopause,” the authors concluded, “further research to examine the safety of ovarian conservation for young women with early stage endometrial cancer is clearly warranted.” They also emphasized that a woman’s options should be carefully discussed with her before deciding to undergo oophorectomy.

Costs Force Some Cancer Survivors to Pass on Health Care

Confronting the Cost of Cancer: Two New Reports

To assist people with cancer as they navigate the difficult and often emotional issues associated with the high costs of their health care, the American Society of Clinical Oncology (ASCO) last week released Managing the Cost of Cancer Care. This booklet has information about what patients can expect and offers suggestions for communicating effectively with their doctors about the costs. There is also a list of organizations that help patients facing financial challenges and a section on health insurance.

A second report out last week, Spending to Survive: Cancer Patients Confront Holes in the Health Insurance System, concludes that too often the health insurance system fails people when they need it most—when they are sick. The study, by the American Cancer Society and the Kaiser Family Foundation, profiles 20 patients and illustrates their difficulties in maintaining affordable health insurance and paying for their health care. An accompanying video can be viewed here.

Economic considerations are forcing an estimated 2 million cancer survivors to go without medical care, such as prescription medications, particularly survivors who are Hispanic or African American, NCI researchers report.

According to the results of a study presented last week at the American Association for Cancer Research Science of Cancer Health Disparities conference, nearly 1 in 10 cancer survivors don’t get prescriptions filled, nearly 8 percent pass on what they believe to be necessary general medical care, more than 11 percent skip needed dental care, and approximately 3 percent forgo mental health services because they are too costly.

That may mean going without, or significantly delaying, such care, explained the study’s lead author, Dr. Kathryn Weaver, a cancer prevention fellow in NCI’s Division of Cancer Control and Population Sciences. The results were not solely explained by access to health insurance. “There are significant out-of-pocket expenses, even for those with insurance,” Dr. Weaver said.

To conduct the study, the research team used 2003–2006 data from the CDC’s National Health Interview Survey (NHIS). They identified more than 6,600 cancer survivors, the large majority of whom were white, and compared them with more than 104,000 people who had no history of cancer. Compared with non-Hispanic whites, Hispanic and African American survivors were significantly more likely to forgo dental care and prescription medications, although, after adjusting for several variables, the disparity was reduced or eliminated. The NHIS is constructed to be representative of the U.S. population, allowing the researchers to arrive at the larger estimate of 2 million survivors who may forgo care due to cost concerns.

While data are not yet available for 2008, said Dr. Weaver, the recent economic downturn will likely make things worse.

“We know that one of the strongest predictors of forgoing care was not having health insurance coverage,” Dr. Weaver said. “If people lose their jobs and, as a result, their health insurance coverage, then the proportion forgoing care is likely to increase.”

Engineered Immune Cells Shrink or Eradicate Large Tumors in Mice

Researchers led by Dr. Carl June at the University of Pennsylvania in collaboration with scientists from NCI’s Center for Cancer Research have created genetically engineered human T cells (a type of immune-system cell) that can recognize and kill cancer cells expressing the protein mesothelin on their surface. Mesothelin is overexpressed in several cancer types that are highly resistant to traditional anticancer treatments, including mesothelioma (cancer of the lining of the chest or abdomen) and pancreatic, ovarian, and non-small cell lung cancer.

In a study published online February 9 in the Proceedings of the National Academy of Sciences, the researchers used a virus to transfer DNA encoding an engineered T-cell receptor into normal T cells. The engineered receptor consists of a protein that recognizes mesothelin attached to signaling proteins that cause the T cells to multiply and then search for and destroy tumor cells bearing a mesothelin target.

In cell-culture experiments, the engineered receptor was successfully expressed by the T cells. These immune cells were then able to identify and kill cancer cells that expressed mesothelin. The engineered T cells did not kill cells that did not express mesothelin.

The researchers implanted mice with mesothelioma cells that produced tumors. When the investigators injected the mice with the engineered T cells, the tumors shrank or were eradicated. One engineered T cell was capable of killing approximately 40 tumor cells, and the T cells persisted in the blood for several weeks after injection.

“Small doses of these cells may have potential in treating patients with large tumors. Clinical trials are being developed to investigate this approach in patients with mesothelioma and ovarian cancer,” said Dr. June in an accompanying press release.

Director's Update

Budget Proposal Highlights Progress and Opportunities in Cancer Research

Dr. John E. Niederhuber Dr. John E. Niederhuber

Last week NCI released The Nation's Investment in Cancer Research, an annual report intended to directly inform the President about the progress and opportunities in our continuing efforts against cancer and to justify the administration’s budget request to Congress for an additional $2.1 billion to fund the Nation’s battle against cancer.

At a time of great economic challenge, the report, which is often referred to as the “bypass budget,” demonstrates how NCI’s deep commitment to outstanding science benefits all Americans. As the 2010 report shows, cancer is a model for studying the biology of all diseases. It can also inform our thinking about the delivery of health care, the development of electronic medical records, and a health care system based on the uniqueness of each individual that employs a new generation of targeted therapies.

The Nation's Investment offers NCI’s professional judgment on strategic programs that could hasten our research progress against cancer while also bringing new therapies, earlier detection, and better methods of preventing cancer to all people.

There is much work to be done. The burden of cancer is rising around the world, and by the year 2010, cancer is expected to replace heart disease as the number-one killer. The Nation's Investment aims to be realistic while also showing how additional investments could be used optimally in the future.

Cover art for The Nation's Investment in Cancer Research

For fiscal year (FY) 2010, NCI’s proposed budget to sustain our current level of activities is approximately $5.1 billion, while the proposal to accelerate progress is an additional $2.1 billion. By comparison, NCI’s FY 2008 budget was approximately $4.8 billion. Though we have operated with what has essentially been a flat budget for the last 5 years, we have actually experienced a significant budgetary decline due to biomedical inflation. When you account for this inflation over the last 10 years, our 2008 appropriation actually represented a purchasing power equivalent to $3.5 billion.

This lost purchasing power has had serious consequences for the cancer research community and, by extension, our patients who carry this burden. In particular, we are deeply concerned about how these changes will affect the next generation of scientists, who are critical for maintaining our nation’s position as a global leader in science, and whose important work is an integral part of our economy.

Were it to receive additional funding, NCI’s first job would be to help increase America’s research capacity by funding scientists, fostering the next generation of researchers, and supporting the development of technology and infrastructure. The report also details how NCI strives to put its science to work for patients, such as our expanding drug discovery platform.

In an era when research is unearthing seemingly unlimited molecular targets and causal pathways in cancer, we must make sound decisions about which ones to pursue and then move agents that target them efficiently into development. NCI is already focusing on ways to enhance the entry of early stage drug candidates into the therapeutics pipeline.

Without question, while there are many needs for increased investment, I believe the greatest is the need for new infrastructure that can optimize translational research in this era when disease and patients are being matched with solutions of highly specific agents.

The Nation’s Investment is an excellent resource for identifying NCI’s priorities and getting a glimpse of the important work on the horizon. But even as we focus on budgets and resources for current and soon-to-be-launched projects, we have to ponder the longer term and investigate possible new directions and avenues for progress.

With this in mind, last month NCI’s Executive Committee convened a group of renowned scientists, some of whom represented disciplines that have not traditionally studied cancer, to consider NCI’s future directions. The meeting, “Conversations about the Future of Cancer Research,” produced many provocative discussions, ranging from how cellular architecture may influence cancer risk to the role of bioenergetics and environmental stress on tumor development. Among the ideas discussed at the meeting, there was a consensus that the tumor microenvironment warrants additional attention.

It was gratifying to witness the prolific exchange of scientific ideas. In fact, several participants said they had discovered new perspectives on their life’s work.

At a time when fresh thinking is in demand, this couldn’t have been a better meeting. We are all energized. Both the retreat and The Nation’s Investment demonstrate NCI’s best efforts to generate the new ideas needed to continue our momentum in understanding cancer and translating the science into better care for patients.

Dr. John E. Niederhuber
Director, National Cancer Institute

A Conversation With

A Conversation with…Dr. Joe Harford

Dr. Joe Harford is director of NCI’s Office of International Affairs (OIA), which coordinates and oversees many of NCI’s internationally focused outreach activities, including the Middle East Cancer Consortium (MECC).

On February 13, the MECC Board of Governors will meet on the NIH campus. Coupled with the meeting will be the launch of an art exhibit in the NIH Visitor Center that will include drawings by children with cancer from the U.S. and four MECC regions.

Dr. Joe Harford Dr. Joe Harford

MECC has quite a history. How was it initially formed?
The launch of MECC occurred in 1996, when NCI assisted in bringing parties in the Middle East together to form this important consortium. MECC initially consisted of Cyprus, Egypt, Israel, Jordan, and the Palestinian Authority. Later, Turkey joined the Consortium. So you had a group with long histories of antagonism among its members—the Cypriots and the Turks, and Israel and three Arab neighbors, with whom three wars have been fought over the past 60 years. As the most recent conflict in Gaza graphically demonstrates, tensions in the region still run high.

Clearly the Consortium’s work had to be prioritized. Where have MECC’s efforts been focused?
At its inception, MECC members recognized that data on cancer incidence and outcomes in the jurisdictions covered by the new alliance were sketchy at best. So the members determined that a joint project on cancer registry would be the most worthwhile place to begin. With NCI support, individuals from all of the MECC regions were trained, side-by-side, and they worked collaboratively on establishing a common set of standards for cancer registry.

A milestone in these efforts came with the publication of an NCI monograph in which cancer incidence in four populations in the region were compared with U.S. incidence data derived from NCI’s SEER database. The Consortium members are now exploring what collaborative research projects should be undertaken based on this registry data.

International Cancer Initiative Works to Combat Obesity

February 4, 2009, was World Cancer Day. The International Union Against Cancer (UICC) used the day to launch a year-long, worldwide effort to combat obesity, a significant cancer risk factor. The campaign’s focus will be to work with parents, teachers, and decision makers around the world to encourage children to eat a healthy diet, be physically active, and maintain a healthy body weight.

Is there interest among MECC members to pursue initiatives that can have a more immediate impact on patient care and outcomes?
Absolutely. One of the most significant challenges facing the cancer care systems in the Middle East is late diagnosis, which diminishes the likelihood of treatment being curative and makes palliative care more imperative. So for its second joint program, MECC is working to improve palliative care in the region.

In addition to conducting an inventory of the available palliative care services in MECC jurisdictions, several successful workshops have been held to build capacity for palliative care delivery. Individuals from MECC jurisdictions have also completed common course work and bedside training at Calvary Hospital in New York. And OIA is supporting a visiting program for Palestinian and Israeli nurses in conjunction with the U.S. Oncology Nursing Society and the Institute for Nursing Healthcare Leadership.

These efforts have borne fruit. In the West Bank, for instance, one of the alumni of NCI/MECC training activities launched the Al-Sadeel Society, the first Palestinian society focused on palliative care for cancer patients. NCI is continuing to support training for Palestinians, with additional activities planned this year for Ankara, Cairo, and Jerusalem, in addition to New York City and Boston.

Is this simply NCI facilitating partnerships, or is it something more than that?
I really believe that MECC is a momentous achievement. It’s a demonstration that peaceful cooperation in the Middle East is both possible and beneficial. For the United States, MECC provides a shining example of what has been termed “health diplomacy,” or fostering peace by helping to improve the health of the people in MECC regions.

Recently, the concept of health diplomacy was resoundingly endorsed by the Institute of Medicine, which called for the new administration to expand the United States’ commitment to improving global health.

And really, that’s what NCI is doing with MECC. For a dozen years, we have been providing support for cancer research capacity in the region and improving cancer care. In essence, MECC operates on the principle captured in an ancient Middle Eastern saying, “The enemy of my enemy is my friend.” We are helping MECC members work together as friends against the common enemy that is cancer.

Spotlight

Matters of the Heart: Why Are Cardiac Tumors So Rare?

Do a Google or PubMed search for “cardiac tumor,” and your results will be littered with individual case reports and little more. There are no clinical trial results, meta-analyses, or treatment guidelines.

Because, although the heart may be the ultimate emblem of love, compassion, and chocolate-themed holidays, it also has another distinction: a near immunity to cancer. And given the heart’s importance in the body, that’s a fortunate fact of life.

However, it does raise the question: Why is this large and infinitely important component of anatomy such an inhospitable host to the leading cause of mortality for those aged 85 and younger? The answer, it appears, can be found in the highly specialized and most abundant cell in this muscle-laden organ, the cardiac myocyte.

A metastatic melanoma tumor in the left ventricle, just prior to surgical removal. Image courtesy of Dr. Robert J. Cusimano. Photo by Win McNamee. A metastatic melanoma tumor in the left ventricle, just prior to surgical removal. Image courtesy of Dr. Robert J. Cusimano.

Few, but Deadly

Cardiac primary tumors, those originating in the heart itself, are extremely rare. In published autopsy series, the high-end incidence of such tumors is about one quarter of one percent. The majority of diagnosed cardiac tumors are benign. In adults, a somewhat mushy, gelatinous type called a myxoma is the most common; in infants and children, rhabdomyomas predominate, typically associated with the syndrome tuberous sclerosis.

According to Dr. Robert J. Cusimano, a cardiac surgeon at Toronto General Hospital, malignant heart tumors are most often metastases from primary tumors in nearby organs, such as the kidneys or lungs.

“If there are metastases to the heart, the prognosis is pretty bad,” said Dr. Cusimano, who lightheartedly refers to himself as a “cardiac oncologist,” because patients with these tumors are often referred to him. Even then, his entire division may see only 12 benign tumors in a given year, while he is personally involved with about 5 to 10 cardiac cancer cases per year, of which one or two are primary malignancies.

Angiosarcomas are the most common malignant primary cardiac tumor. According to recently published case reports, including one published early online last month that Dr. Cusimano co-authored, a treatment approach that’s been employed with some success is chemotherapy and/or radiotherapy to shrink the primary tumor and eliminate any micrometastases, followed by surgery to remove the primary tumor.

The Tell-Tale Cell

Unlike other damaged organs, the heart seems mostly incapable of mending injured tissue. And that, according to leading cardiac researchers, is because the cells that compose the muscle itself, cardiac myocytes, are terminally differentiated.

In other words, these cells reach a point very early on in a person’s life where they permanently exit the cell cycle and stop dividing. After that, further growth occurs by expansion in cell size, not through cell division. This differs, for instance, from the epithelial cells that line other organs, which, in response to certain stimuli, actively divide and, when necessary, grow in number.

This “very tight cell cycle control of cardiomyocytes” acts as a double-edged sword, explained Dr. Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease at the University of California, San Francisco. Not only does it “prevent them from ever re-entering the cell cycle to proliferate and repair damaged tissue,” but it may also explain why “they are so resistant to tumor formation,” he said.

With so little proliferative activity, added Dr. John E. Tomaszewski, from the Department of Pathology and Laboratory Medicine at the University of Pennsylvania Medical School, “the opportunity for abnormalities in cell cycle kinetics which characterizes tumors in so many other body sites is just not an issue in the heart.”

Given their extreme rarity, there is little in the way of any organized effort to further research on how and why cardiac tumors arise or how best to treat them. For now, Dr. Cusimano believes, the wisest avenue to help improve outcomes is to funnel patients to centers that have experience treating patients with cardiac tumors.

Routinely sending patients to these hospitals will ensure that “surgeons and oncologists can get more experience with these cases,” Dr. Cusimano said. “That’s the only way we can move forward with these types of cancers.”

—Carmen Phillips

Profiles in Cancer Research

Dr. Craig Jordan

Dr. Craig Jordan Dr. Craig Jordan

Professor of Medicine, Department of Hematology/Oncology, James P. Wilmot Cancer Center

Dr. Craig Jordan has been studying human leukemia stem cells for a decade, using molecular and genetic analysis to identify characteristics that may extend the capabilities of personalized medicine. He is a patient, diligent pioneer in this effort. Adding to the challenge, he is working against a foe that is surprisingly elusive. For leukemia stem cells are in effect shape shifters, modifying their genetic code not only from person to person, but within a person and over the course of time.  

“This is a very multidisciplinary problem,” he explained. “The last 10 years or so have been a really interesting time, and we’ve made a lot of progress. But I would say that we probably only have one chapter of the book on leukemia stem cells under our belt. There’s still a lot to learn.”

As a part of the University of Rochester’s James P. Wilmot Cancer Center, Dr. Jordan and his lab members collaborate closely with clinical research staff on site, conferring with them every day in what he describes as a highly collegial environment. “When you’re around the physicians who have these horribly sick patients, it’s hard not to want to do something,” he explained. “These are very bad diseases.”

Dr. Jordan briefly considered a career in medicine as a young man growing up in California. But after working in a research lab for several years after college, he decided that graduate school was a better fit. He entered the doctoral program at Princeton University with an interest in hematopoietic stem cells and went on to a fellowship at the Whitehead Institute. Several years after that were spent working in the biotech industry before he rejoined the academic ranks in 1997 at the University of Kentucky as an assistant professor of medicine.

Just a few years earlier, an important paper had been released in Nature by Dr. John Dick and colleagues. “That paper put leukemia stem cells on the map, in terms of characterization,” he said. “I was undifferentiated, if you will, at the time. And in Kentucky, I was working for the first time at a cancer center with physicians who were dealing with cancer patients on a daily basis. So the proximity to the clinical world and these newly characterized leukemia stem cells caught my attention.”

“The field was still very, very new,” recalled Dr. Monica Guzman, who came to the University as a graduate student from the Mexican city of León, choosing Dr. Jordan’s lab for her research. “We were essentially taking a shot in the dark, and there were a lot of people who questioned the concept of targeting leukemia stem cells. But now, things have turned out very well, and I think I made an excellent decision to join him in this project.”

Dr. Guzman says that Dr. Jordan’s patience and his ability to understand what each member of his laboratory needs to help them succeed have been special gifts to her in her career.

“His door is always open,” she said. “He’s given me a lot of independence in my research, but has offered more hand-holding for others when he thought that they needed it.”

Their big breakthrough came in 2001, when they released an article in Blood showing that the nuclear-factor kappaB (NFkB) molecular switch is activated in acute myelogenous leukemia stem cells. It revealed a vulnerable target for the disease. Now, Dr. Jordan is working with a company to test a plant-derived drug called parthenolide, which targets NFkB, in a phase I clinical trial. A number of other small molecules that target additional leukemia stem-cell characteristics are in the pipeline.

His ability to work so successfully with collaborators in government and with industry, including NCI’s RAID program, is uncommon for a basic scientist, said Dr. Allan Mufson, chief of the Cancer Immunology and Hematology Branch in NCI’s Division of Cancer Biology. “This puts him at the forefront of basic scientific investigators who are not clinicians, who have that stick-to-it-iveness to push something forward and get something in testing, because that’s difficult to do.” 

Despite all of the success, Dr. Jordan acknowledged that there’s still a long row to hoe. “Nobody has really proven, yet, that we’ll be able to successfully treat more patients by targeting these things,” he said. “I hope that we’ll be able to really understand whether this treatment strategy is going to work within the next 5 to10 years, and I think that’s about the time frame that we’ll need to really figure it out.”

Brittany Moya del Pino

Featured Clinical Trial

Enhancing Cancer Information Materials with Multimedia

Name of the Trial

Randomized Study of a Cancer Information Service Research Consortium Multimedia Educational Program in Patients with Early Stage Prostate or Breast Cancer (AMCCRC-08-0498). See the protocol summary.

Dr. Alfred Marcus Dr. Alfred Marcus

Principal Investigator

Dr. Alfred Marcus, AMC Cancer Research Center

Why This Trial Is Important

NCI’s Cancer Information Service (CIS) provides cancer-related information to the public through the 1-800-4-CANCER toll-free number. In addition to answering questions about cancer, the CIS routinely mails relevant NCI print publications to callers. Researchers are testing in three separate trials whether adding a multimedia educational program to these print materials can help patients with prostate cancer (Trial #1) or breast cancer (Trial #2) make informed treatment choices, or help breast cancer patients prepare for life after treatment (Trial #3).

Patients with newly diagnosed prostate or breast cancer or who are finishing or have recently completed treatment for breast cancer and who call the CIS for information will be invited during the call to participate in one of these trials. Participants will be randomly assigned to receive standard print materials or the same print materials plus a related multimedia program. “We think that the multimedia programs will be more effective in empowering patients to make informed decisions about their cancer treatments and in helping them adjust to life post-treatment,” said Dr. Marcus.

The multimedia programs include a virtual library, videos of specialists discussing the pros and cons of different treatment options or life after treatment for cancer, a notebook feature to store text information, a doctor-patient communication tutorial to help users frame questions for their health care team, and, for newly diagnosed patients, a tool to help them evaluate different treatment options.

Patients will be contacted 2 and 9 months after receiving the materials to assess their cancer-specific distress, emotional quality of life, physical functioning, and other outcomes.

Patients finishing treatment for breast cancer will also be randomly assigned to receive either a call back from the CIS 7 to 10 days after their first call or no further contact. As noted by Dr. Marcus, “If we can show through this trial that this new call-back strategy is acceptable and provides a benefit to callers, this could open up exciting new opportunities for extending the service of the CIS.”

For More Information

See the lists of entry criteria and trial contact information.

An archive of "Featured Clinical Trial" columns is available at http://www.cancer.gov/clinicaltrials/ft-all-featured-trials.

Community Update

New Reporting System Under Way for NCI Clinical Trials

Fulfilling a key recommendation from the NCI Clinical Trials Working Group (CTWG), all clinical trials that receive NCI funding will be registered in a central database as part of the new Clinical Trials Reporting Program (CTRP). The phased launch of this program calls for NCI-designated Cancer Centers to begin registering new intervention trials in October 2009, with other NCI grantees following their lead in January 2010.

This rule applies to any intervention study opened to accrual after January 1, 2009.  In 2010, observational, ancillary, and correlative studies will be included.
 
“It is clearly useful to identify such research, but such a prioritization process can only rationally begin with a shared foundation of comprehensive, up-to-date information,” said CTWG chair Dr. James Doroshow.

The phased launch of CTRP began in early January with five pilot sites: Dana-Farber/Harvard Cancer Center, Mayo Clinic Cancer Center, Wake Forest Comprehensive Cancer Center, Robert H. Lurie Cancer Center at Northwestern University, and the St. Jude Children’s Research Hospital. A larger group will join them in early April, with all grantees scheduled to follow by this fall. The goal is for the CTRP to eventually include all trials, regardless of funding source.

While no grantees will be exempt from registration, three NCI organizations—NCI’s Center for Cancer Research, Cancer Therapy Evaluation Program, and Division of Cancer Prevention—will fulfill this task on behalf of their grantees by entering existing trial information directly into the CTRP. Clinical trial administrators will be able to search the CTRP Web site to find out if their trial has already been registered.

“We want to streamline the process and minimize the reporting burden on our investigators,” said John Speakman, associate director for clinical trials products and programs at the NCI Center for Biomedical Informatics and Information Technology (CBIIT). Federal requirements preclude CTRP from registering trials on ClinicalTrials.gov on behalf of the grantee. However, CTRP staff will summarize data from the trial protocol and other submitted materials to develop a formatted file that the submitting organization can provide to ClinicalTrials.gov.

Addison Greenwood

Cancer.gov Update

New Dietary Data Available Online

NCI researchers have developed a new method for estimating long-term dietary intakes in the U.S. population and have applied it to National Health and Nutrition Examination Survey (NHANES) data, the primary source of diet and health data for the U.S. population. Until recently, efforts to capture food intakes over time have been limited at best. This new method enables researchers to monitor people’s diets relative to recommendations and to assess the scope of dietary deficiencies and excesses.

Tables presenting estimated means and percentiles of food intakes for a range of sex-age groups in the U.S. population between 2001 and 2004 are available online. NCI staff shared these data with the Federal Dietary Guidelines Advisory Committee, whose members were interested to learn the extent of imbalances in the U.S. diet.

Further details about the NCI method of usual intake estimation, statistical methods used, and a copy of the 2003–2006 NHANES Food Frequency Questionnaire can be found online.

NHANES Dietary Web Tutorial Guides Data Users

NHANES logo

NCI, the National Center for Health Statistics, and the U.S. Department of Agriculture recently developed a Web-based tutorial to promote broader and more proficient use of NHANES diet and health data. This is one of a series of NHANES tutorials. Previous tutorials are already used widely, including by universities in their public health courses.

NHANES dietary data are especially complicated because data from the 24-hour recalls, food frequency questionnaire, and dietary supplement questionnaire each measure different aspects of dietary intake, cover different time periods, and are collected differently.

The NHANES Dietary Web Tutorial guides users through the data and offers instructions on how to retrieve dietary data files and supplementary information; correctly prepare a dietary dataset and create appropriate food and nutrient variables; and correctly conduct basic as well as more advanced analyses. Three courses have been accredited to offer continuing education units.

Notes

NCI Lecture Series Features Dr. Napoleone Ferrara

Dr. Napoleone Ferrara Dr. Napoleone Ferrara

NCI’s Center for Cancer Research (CCR) recently launched its “Eminent Lecture Series,” a collection of presentations by prominent scientists around the country who work in cutting-edge research areas and come to NIH to stimulate a scientific exchange of ideas. 

Dr. Napoleone Ferrara, a fellow at Genentech, Inc., will present the series’ next lecture on February 23 at 3:00 p.m. in Lipsett Amphitheater on the NIH campus in Bethesda. The title of Dr. Ferrara’s talk is “Novel Insights on the Regulation of Angiogenesis by VEGF-A and other Mediators.” Dr. Ferrara was the recipient of the American Society of Clinical Oncology 2007 Science of Oncology Award for his groundbreaking research, including being the first to identify the vascular endothelial growth factor (VEGF) protein, a major regulator of angiogenesis. The lecture series is free and open to the public.

Bridge Awards Available from SBIR

The deadline for applications to NCI’s Small Business Innovation Research (SBIR) Phase II Bridge Award program is February 27.

The Bridge Award will support small businesses that seek additional NIH funding for projects applicable to cancer therapies and cancer imaging technologies, bridging the gap between the end of the SBIR Phase II award and commercialization.

More information on the award and how to apply is available online.

NCAB Convenes Its First Meeting of 2009

The National Cancer Advisory Board’s (NCAB) first meeting of the year was held at the NIH campus on February 3 and 4. In addition to NCI Director Dr. John Niederhuber’s update on the NCI budget and the recent Executive Committee Scientific Retreat, NCAB members heard presentations on a variety of issues, including ways to enhance peer review, the implementation of recommendations from the Clinical Trials and Translational Research Working Groups, and an update on NCI’s tobacco control efforts and activities.

Another highlight of the meeting was a presentation by Lenora Johnson, director of NCI’s Office of Communications and Education (OCE). Ms. Johnson briefed the board on OCE’s organizational structure and vision for moving forward on a variety of fronts, including social media, multiplex communications, and partnerships and outreach.

A full copy of the meeting agenda and a videocast of the 2-day meeting can be viewed online.