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January 25, 2011 • Volume 8 / Number 2

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Human chromosomesGenetic Study Reveals Clues to Pancreatic Neuroendocrine Tumors

Researchers at the Johns Hopkins Kimmel Cancer Center have sequenced DNA from patients with an uncommon form of pancreatic cancer to produce the first overview of the genetic basis of the disease, called neuroendocrine tumors. The investigators identified several genes that may provide prognostic information, as well as mutations in genes in a signaling pathway for which targeted therapies currently exist. Read more > >


A Conversation with Dr. Angela Mariotto and Dr. Martin Brown on the Rising Costs of Cancer Care

Dr. Angela Mariotto and Dr. Martin BrownThe two researchers from NCI’s Division of Cancer Control and Population Sciences spoke about a study published earlier this month in JNCI and how we may be able to address the looming issue of caring for a growing population of cancer survivors. Read more > >




  • FDA Update

    • FDA Updates Safety Review of Diabetes Drug for Possible Cancer Risk
  • Notes

    • In Memoriam: Arthur Schatzkin, Branch Chief in DCEG
    • New Program Aims to Help Businesses Navigate Regulatory Clearance for Products
    • New Issue of CCR Connections Published
    • State Cancer Legislative Database Adds Obesity Prevention

Selected articles from past issues of the NCI Cancer Bulletin are available in Spanish.

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Featured Article

Genetic Study Reveals Clues to Pancreatic Neuroendocrine Tumors

Machines used to sequence DNA Machines used to sequence DNA for the study at Johns Hopkins (Photo courtesy of Dr. Nickolas Papadopoulos)

Researchers at the Johns Hopkins Kimmel Cancer Center have sequenced the genes of patients with an uncommon form of pancreatic cancer, producing the first overview of the genetic basis of the disease, called neuroendocrine tumors. The investigators identified several genes that may provide prognostic information, as well as mutations in genes in a signaling pathway for which targeted therapies currently exist. Their findings appeared online in Science Express on January 20.

Patients whose tumors had mutations in three commonly mutated genes lived longer than patients without these mutations, the researchers found. In addition, some patients had mutations in genes that encode proteins in the mTOR pathway. These individuals could be candidates for drugs such as rapamycin (everolimus), which block growth-promoting signals through the mTOR pathway.

“It’s really exciting that some potential clinical applications have emerged from our first report on this disease,” said lead investigator Dr. Nickolas Papadopoulos, who directs translational genetics at the Johns Hopkins Ludwig Center for Cancer Genetics & Therapeutics. But more follow-up work is needed, he noted, such as a clinical trial to evaluate the use of mTOR inhibitors in selected patients.

“This study is a very important step forward,” said Dr. Philip A. Philip, who studies cancers of the pancreas at the Barbara Ann Karmanos Cancer Institute in Detroit, MI, and was not involved in the research. “The results underscore the fact that the only way we can make any headway in our search for more effective therapies is to understand disease biology at a level that is much higher than we know so far—and that applies to all cancers.”

Pancreatic neuroendocrine tumors, also called islet cell tumors, make up less than 5 percent of all pancreatic cancers. These patients have a better prognosis than patients who develop what is most commonly called pancreatic cancer, ductal adenocarcinoma of the pancreas. But some neuroendocrine tumors grow silently and are discovered only after they have spread to other organs, so more effective treatments beyond surgery are needed.

To gain insights into the genetic basis of the tumor, the researchers sequenced nearly all of the protein-coding genes in tumor and normal tissue samples from 10 patients with pancreatic neuroendocrine tumors. The patients did not have an inherited form of the disease.

The three most commonly mutated genes in the 10 tumors—MEN-1, DAXX, and ATRX—all play a role in the packaging of DNA. Known as chromatin remodeling, this is an epigenetic process that controls the activity of genes without causing changes in DNA sequence. But mutations in genes involved in chromatin remodeling may affect the regulation of genes elsewhere in the genome.

“We are seeing a connection between genetics and epigenetics, and also how the genetics may actually confer the epigenetic changes we’ve known about for so long,” said Dr. Papadopoulos. His group recently published genome studies of ovarian cancer and medulloblastoma, and in both cases mutations were found in genes involved in epigenetic processes. (See “Seeking Better Treatments for Brain Tumors in Children” in this issue.)

The stability of the chromatin is essential for the normal expression of genes, noted Dr. Laufey Amundadottir of NCI’s Division of Cancer Epidemiology and Genetics (DCEG), who co-led a genome-wide association study of pancreatic cancer. “When chromatin is not maintained in its original form,” she explained, “gene expression can go awry.”

After identifying gene mutations in the 10 samples, the Hopkins team sequenced these genes in samples from 58 additional patients with pancreatic neuroendocrine tumors. Among the 68 tumors, 44 percent had somatic (non-inherited) mutations that inactivated MEN-1, and 43 percent had mutations in either DAXX or ATRX, which produce proteins that are components of the same molecular complex.

Patients with mutations in MEN1 or DAXX/ATRX tended to live longer than patients without the mutations. The difference was particularly striking among patients who had metastatic disease and whose tumors had mutations in both MEN1 and DAXX/ATRX. These patients all survived at least 10 years, whereas more than 60 percent of the patients without the mutations died within 5 years of diagnosis.

Patients with mutations in MEN1 and DAXX/ATRX may have a biologically distinct subtype of pancreatic cancer, the researchers suggested, and this could explain the difference in survival.

Another category of tumors—14 percent of the total—were those with mutations in mTOR pathway genes, including TSC2, PTEN, and PIK3CA. “This finding obviously needs to be validated in large clinical trials, but it is an exciting example of ‘personalized medicine,’” said co-author Dr. Ralph Hruban, who directs the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins.

Additional evidence that mTOR is a relevant target for treating some patients with pancreatic neuroendocrine tumors comes from several recent clinical trials, noted Dr. Jack Welch of NCI’s Division of Cancer Treatment and Diagnosis (DCTD). Preliminary results reported last year indicated that everolimus improved progression-free survival in a subset of patients, while another study suggested that everolimus can treat patients whose disease progresses despite chemotherapy.

Based on these results, the NCI Clinical Trials Cooperative Group Program has launched a national phase II clinical trial (CALGB-80701) of everolimus with or without bevacizumab in patients with locally advanced or metastatic pancreatic neuroendocrine tumors.

Additional studies are under development, noted Dr. Welch. “These trials will include correlative laboratory studies to expand the understanding of the underlying biology of this disease in patients like those in the Johns Hopkins study,” he said.

In 2008, the Johns Hopkins team surveyed tumors from patients with pancreatic ductal adenocarcinoma. With the new results, it is now clear that there are some obvious genetic differences between this disease and pancreatic neuroendocrine tumors. For example, fewer genes were mutated in pancreatic endocrine tumors than in pancreatic ductal adenocarcinomas, and the most commonly mutated genes in each type were different.

One possible explanation, the researchers suggest, is that mutations in each of these cancers may arise through different mechanisms, perhaps due to exposure to different environmental carcinogens or through the action of different pathways for repairing damaged DNA.

“This study really demonstrates the power of new DNA sequencing technologies,” said Dr. James V. Tricoli of NCI’s Cancer Diagnosis Program, who was not involved in the research. “As more groups start to use these approaches, we are going to identify additional mutations that can not only subcategorize tumors but also reveal to us better ways to treat these patients—and that’s the most important outcome.” 

Edward R. Winstead

Cancer Research Highlights

Trial Suggests New Treatment Option for Gastrointestinal Stromal Tumors

The targeted therapy sorafenib (Nexavar) may be a treatment option for patients with gastrointestinal stromal tumors (GIST) whose cancers no longer respond to two FDA-approved therapies, researchers reported last week at the 2011 Gastrointestinal Cancers Symposium in San Francisco.

In a 38-patient phase II clinical trial, 13 percent of patients whose tumors had developed resistance to imatinib (Gleevec) and sunitinib (Sutent) had a partial response (tumor shrinkage of 50 percent or more) after taking sorafenib, and 55 percent experienced disease stabilization (no further tumor growth) with the drug. Median progression-free and overall survival was 5.2 and 11.6 months, respectively. After 1 year, 44 percent of patients were still alive; after 2 years, survival had dropped to 21 percent.

Sorafenib has multiple molecular targets, including mutated forms of several tyrosine kinases—disregulated forms of which are implicated in a number of cancers—that are known to be insensitive to imatinib and sunitinib, explained the trial’s lead investigator, Dr. Nicholas Campbell from the University of Chicago, during a press briefing. The trial protocol was amended early on to require that participants have GIST that is resistant to both imatinib and sunitinib. Overall, six patients in the trial were resistant to imatinib and 32 were resistant to both.

More than 60 percent of the patients in the NCI-supported trial had to have their sorafenib dose reduced because of side effects, including large increases in blood pressure and serious skin rashes, although reducing the dose did not appear to alter the drug’s efficacy, Dr. Campbell added.

The results show that sorafenib has “definite clinical activity” in patients with GIST whose tumors have developed resistance to imatinib and sunitinib, he concluded, adding that further studies of sorafenib as a therapy for GIST are warranted. An exploratory analysis of patients in the trial is being conducted to determine whether mutations in two tyrosine kinases, PDGF and KIT, correlate with response to sorafenib.

Gene Test for Risk of Colorectal Cancer Recurrence Validated

An experimental genetic test designed to assess the risk of colorectal cancer recurrence in patients with early-stage disease has been validated for a second time, researchers reported last week at the 2011 Gastrointestinal Cancers Symposium in San Francisco. The test, called ColoPrint, provides a risk score based on the activity of 18 genes. The development of the test and its initial validation are described in a report published last year.

Most patients with stage II colorectal cancer are treated with surgery alone. But about 20 percent of these patients experience a recurrence and could potentially benefit from adjuvant (post-surgical) chemotherapy to reduce this risk. The new study showed that the gene classifier test could “facilitate the identification of patients who might not need chemotherapy,” said Dr. Robert Rosenberg of the University Hospital at the Technical University, in Munich, Germany, during a press briefing. The study was funded in part by Agendia, the manufacturer of the test.

Previous attempts to use pathologic and clinical factors to predict prognosis have been unsuccessful. In the current study, the researchers used the ColoPrint test to analyze tumor tissue from 233 patients who had undergone surgery for stage II or stage III colorectal cancer at the University Hospital in Munich. Based on patterns of gene activity in the tumors, the gene classifier produces a score indicating low or high risk of recurrence.

The researchers then compared the risk scores of the 135 stage II patients with their outcomes. The gene classifier identified 73 percent of the stage II patients as low risk, and 5 percent of this group experienced a recurrence within 5 years or more. The test identified the remaining 27 percent of stage II patients as high risk, and 20 percent of these patients did have a recurrence during a median follow-up period of more than 8 years. The performance of the gene classifier seemed to be independent of clinical risk factors, Dr. Rosenberg explained.

A third validation study, the PARSC (Prospective Analysis of Risk Stratification by ColoPrint) trial, has been launched. This trial, which is sponsored by Agendia, will address the feasibility of using the gene classifier in clinical practice and test whether the ColoPrint assay offers a more accurate risk assessment for recurrence than commonly used clinical parameters.

Newly Discovered Mutations May Help Drive Common Kidney Cancer

Researchers have discovered mutations in a gene called PBRM1 in more than one-third of clear-cell renal cell carcinomas (ccRCC), the most common kind of kidney cancer. In a series of experiments led by Dr. Ignacio Varela of the Wellcome Trust Sanger Institute, an international team of researchers identified PBRM1 as a potential tumor suppressor gene and showed that the loss of the gene’s function may contribute to kidney cells developing the properties of cancer cells, such as uncontrolled cell growth. The findings appeared online January 19 in Nature.

The scientists first sequenced portions of the genome known to produce proteins (called the exome) in seven ccRCC tumor samples and normal tissue from the same patients. They identified 156 mutations in those seven samples, but only mutations in PBRM1 were found in more than one sample. They next sequenced the PBRM1 gene in an additional 257 renal cell carcinoma samples (including 36 non-ccRCC cases) and found mutations in 88 samples (all ccRCC), a frequency that the authors described as “remarkable.”

The researchers also found PBRM1 mutations in breast, lung, kidney, gallbladder, and pancreatic cancer cell lines. Analysis of genetic data from a mouse model of pancreatic cancer indicated that inactivation of the PBRM1 gene may help drive pancreatic tumor development in this model.

Using small interfering RNAs to block PBRM1 activity in ccRCC cells, the researchers were able to increase cell proliferation, cell-colony formation (the ability to grow and divide without physical support), and cell movement, like that required for metastasis. PBRM1 codes for a protein that is involved in chromatin remodeling, a process that allows transcription factors to gain access to DNA that is otherwise tightly packaged with proteins. Analysis of the cell-signaling pathways regulated by PBRM1, the authors wrote, suggests that “PBRM1 activity regulates pathways associated with chromosomal instability and cellular proliferation.” They also noted that several other genes that have been implicated in ccRCC are involved in chromatin remodeling.

“This is very promising, very exciting work,” commented Dr. Marston Linehan, chief of the Urologic Oncology Branch in NCI’s Center for Cancer Research, who was part of the scientific team that identified the tumor suppressor gene VHL, which is the only other gene known to play a role in a large number of ccRCC cases. “This finding leads us potentially into a whole new direction in thinking about the basic aspects of kidney cancer and potential approaches to therapy. It’s possible that mutations in PBRM1 are a critical part of clear-cell kidney cancer and that you need both VHL and PBRM1 to be altered to develop a clear-cell kidney cancer,” he concluded.

Interferon-gamma Promotes UV-Induced Melanoma in a Mouse Model

The immune system protein interferon-gamma may fuel melanoma in mice by promoting the growth, survival, or both of melanocytes, the pigment-producing cells in which melanoma begins. The results, from research aimed at understanding how ultraviolet (UV) radiation from the sun and other sources causes melanoma, appeared online January 19 in Nature. The finding that interferon-gamma promotes melanoma was unexpected because interferon-gamma has been thought to be part of the immune system’s innate defense against cancer.

Researchers led by Drs. Glenn Merlino and M. Raza Zaidi of NCI’s Laboratory of Cancer Biology and Genetics found that UVB radiation (UVB), at doses equivalent to what causes sunburn in human skin, triggered aberrant growth and migration of melanocytes in mouse skin. UVB exposure also persistently activated genes that are known to respond to interferon-gamma, including genes that may help tumor cells evade detection and attack by the immune system. Blocking the activity of interferon-gamma lessened the effects of UVB on the growth and migration of melanocytes.

The team showed that interferon-gamma was being produced by white blood cells known as macrophages, which traveled to the skin after UVB exposure. These macrophages significantly enhanced melanoma tumor growth when the researchers injected them under the skin of healthy mice along with cultured mouse melanoma cells, and this effect was abolished by blocking interferon-gamma activity. The researchers also identified interferon-gamma-producing macrophages in 70 percent of 27 human melanomas they examined, supporting the possibility that interferon-gamma plays a role in this type of cancer not just for mice but also for humans.

Dr. Merlino noted that treatments with high doses of interferons and other cytokines in cancer patients, which are not always effective, can be toxic and are often associated with debilitating side effects. “The new study shows that lower, physiologically relevant levels of interferon-gamma, produced by specific tumor-associated inflammatory cells, can actually support melanoma growth” in mice, he said. Thus, if this holds true in humans, “inhibition of the interferon-gamma pathway may represent a more effective, less toxic immunotherapeutic alternative for treatment of a subset of patients with macrophage-rich melanomas.” Moreover, Dr. Merlino added, inhibiting interferon-gamma immediately after sunburn, an approach that his lab is pursuing, may prove to be an effective preventive strategy against UV radiation-induced melanoma.

Also In the News: Health Disparities Report Shows Colorectal Cancer Screening on the Rise

The CDC recently released the 2011 CDC Health Disparities and Inequalities Report, the first in a series of reports that examine disparities in social and health indicators. The report covers topics ranging from health care access to infant mortality to unhealthy air quality exposure.

One chapter of the report addresses disparities in colorectal cancer screening rates. CDC researchers used data from the Behavioral Risk Factor Surveillance System surveys to look at changes in colorectal cancer screening rates from 2002 to 2008. Overall use of screening tests increased by more than 10 percentage points (from less than 54 percent to more than 64 percent) during that time, the researchers found, but disparities still existed among certain groups. Household income, access to health insurance, and education also influenced these screening rates. For instance, screening increased by only about 4 percentage points among American Indian/Alaska Native populations and by 4.5 percentage points among those without health insurance.

The report states that “differences in health based on race, ethnicity, or economics can be reduced, but will require public awareness and understanding of which groups are most vulnerable, which disparities are most correctable through available interventions, and whether disparities are being resolved over time.”

A Conversation With

A Conversation with Dr. Angela Mariotto and Dr. Martin Brown on the Rising Costs of Cancer Care

Drs. Angela Mariotto and Martin Brown Drs. Angela Mariotto and Martin Brown

A new study from researchers in NCI’s Division of Cancer Control and Population Sciences (DCCPS) published January 12 in the Journal of the National Cancer Institute projects that the cost of caring for the U.S. population of cancer patients and survivors will increase substantially over the next 10 years. The researchers used data on cancer incidence and survival and on care costs by phase of care to develop estimates of the overall cost of care. They found that even if medical costs, cancer incidence, and survival remain static, the rapid aging of the U.S. population will cause the overall cost of care to rise from $125 billion in 2010 to $158 billion by 2020. If costs of care rise by only 2 percent annually, the overall cost of cancer treatment would rise to $173 billion by 2020, an almost 40 percent increase over the course of 10 years. Dr. Angela Mariotto, lead author of the study, and Dr. Martin Brown, chief of the Health Services and Economics Branch in DCCPS, recently spoke about this looming issue and how to address it.

These projected numbers are higher than some others recently published. Why are your estimates different?

Dr. Mariotto: Previous cost estimates have been based on older data. We used the most up-to-date Surveillance, Epidemiology, and End Results (SEER) data, from 2007, and linked SEER-Medicare data, which includes claims through 2006. The population projections we used, from the U.S. Census Bureau, were based on the period of 2006 through 2020.

Our methodology was also better than previous studies because we calculated prevalence and costs by phases of care. Initially, in the first year after a cancer diagnosis, costs are very high. If people die of their cancers, costs go up again sharply in the last year of life. In between the initial period following diagnosis and the last year of life, costs are lower.

Breaking down costs of care this way helps with overall accuracy of the projections and also helps us understand where the money is being spent. For example, one of the results from the study is that costs will likely increase substantially for breast and prostate cancer survivors in the period between diagnosis and the last year of life, simply because those are two of the three most common types of cancer. Costs per patient are very low in the survivor phase, but the fact that we will have such a large number of patients drives up the total cost.

The first generation of baby boomers will turn 65 this year, and people 65 and older have the highest incidence of cancer. Is this aging cohort inflating the costs of cancer care only in the short term?

Dr. Brown: It’s probably true that if we were to project out to, say, 2040, we would see a trend of costs not going up as quickly, or maybe even going down, though the further out you get in these kinds of projections the more uncertainty there is in general. But baby boomers like me may still be around in 2040, so we’re talking about a pretty distant horizon before costs even begin to taper.

We’ve seen an overall decline in cancer incidence as a recent trend. How will this influence your projections?

Dr. Mariotto: The main driver of the rise of medical costs associated with cancer is the aging of the U.S. population. If cancer incidence continues to decline as it has, then that may mitigate the increase in total costs—and we estimate them to be $148 billion in 2020 instead of $158 billion. However, survival has improved in the last decade, and if it continues to improve, that will again increase costs. We are planning to do longer-term prevalence projections in an upcoming study to get a better idea of what year prevalence and costs will begin to decline.

Previous studies have shown that the per-person costs of cancer care are actually higher for people younger than 65 than for older people, probably because doctors tend to use more aggressive care in younger patients compared with the older population. We still need better data to estimate costs in the younger population and are actively planning to gather these data and develop studies to improve cost estimates in the younger population.

These numbers indicate a growing burden on an already strained medical system. Are there any obvious areas of care we could improve in a way that may, at the same time, potentially decrease cost?

Dr. Brown: The idea of comparative effectiveness research has potential in our health care system for improving the quality of care, and perhaps increasing savings. There are a lot of big questions about effectiveness in cancer treatment left to answer. For example, in early-stage prostate cancer, we still haven’t answered in a randomized clinical trial which treatment approach is most effective: radiation, surgery, or watchful waiting.

Then there are related important questions inside of every big question. Say, if radiation therapy turns out to be the best option, there are four or five different kinds of radiation treatment available, and these vary dramatically in cost. If it turned out—and obviously we don’t know this yet—that a less expensive type of treatment is just as good as or even better than some of the more expensive modalities, that would be an example where we could identify savings that will make a real difference for our health care system, because prostate cancer is one of the most commonly diagnosed cancers.

There are many areas of cancer medicine where we still don’t know what the best care really is, or where we do know that the way we’re doing things currently is quite inefficient. I think we literally have to look at the evidence in every area of cancer medicine. We have to know which treatment approaches are more or less effective and then identify changes to improve the quality of care and cancer outcomes.

Sharon Reynolds

The DCCPS researchers have created an interactive tool to help interested individuals explore the data visually. The interactive charts and graphs are available at

A video of Dr. Mariotto and co-author Dr. Robin Yabroff discussing the results of the study is available on the NCI YouTube channel.

Special Report

Can Aspirin Reduce Cancer Risk and Mortality?

Aspirin pills As optimism for aspirin’s apparent anti-cancer effects grows, unanswered questions remain.

The prospect is too enticing to dismiss: a single pill—a cheap one, too—that, when taken regularly, can reduce the risk not only of heart attack or stroke, but also of developing or dying from some types of cancer.

The pill is aspirin, and a host of studies have suggested that it can prevent and possibly reduce the risk of dying from some cancers. The data in support of aspirin’s anticancer effects recently received another boost, with one of the largest analyses to date—a meta-analysis of eight clinical trials involving regular aspirin use, published online December 6 in The Lancet—showing a substantial reduction in mortality for a number of different cancers.

As is often the case, though, the story is not that simple. None of the trials included in the meta-analysis, for example, was designed specifically to assess whether aspirin reduces cancer incidence or mortality. And although many studies, including a few clinical trials, support the notion that aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of developing or dying from some cancers, other studies, including clinical trials, have reached a different conclusion.

It would certainly be welcome news to say this century-old pill may be the next great clinical cancer advance. But at this point, the sentiments among researchers in the field are mixed, and no medical organization has issued guidelines or recommendations on aspirin’s use as an anticancer therapy. For the moment, at least, the emergence of aspirin into a cancer prevention role seems to be on hold.

Lots of Data, but Still Unknowns

The meta-analysis, led by Dr. Peter Rothwell from the University of Oxford, found that after 5 years of follow-up, trial participants who took aspirin daily—regardless of dose—for a mean of 4 years had a 44 percent reduced risk of dying from cancer compared with participants who took a placebo. The largest decrease in risk was for gastrointestinal cancers.

One of the strong points of the meta-analysis, noted Dr. Rothwell, is that it included 20 years of follow-up data for individual participants in three of the eight trials, rather than relying solely on combined data from the original studies. In this subset of patients, there was a 20 percent lower risk of dying from cancer after 20 years, with the largest benefit seen again for gastrointestinal cancers. Overall in the meta-analysis, trial participants who took aspirin had a decreased risk of dying from relatively rarer but highly deadly cancers such as pancreatic and esophageal, as well as from common cancers such as lung and prostate. The longer the duration of aspirin use in the trials, the greater the benefit.

Recently, a similar meta-analysis from the same research team, this one focused specifically on the effect of aspirin use on colorectal cancer, showed large and statistically significant reductions in both incidence and death from the disease. The finding, the study team pointed out, is consistent with results from numerous studies that have shown regular NSAID use reduces or prevents the growth of precancerous growths in the colon.

The mounting evidence of aspirin’s strong anticancer effect is hard to ignore, argued Dr. Rothwell. “At a minimum, in combination with the appropriate screening, the data indicate that aspirin would be highly effective in preventing colon cancer,” he said.

Dr. Rothwell is not alone in his opinion. “I do believe there is a role for using [NSAIDs] at a subtherapeutic level for various types of tumors,” said Dr. Randall Harris from Ohio State University. Dr. Harris led a prospective observational study of participants in the Women’s Health Initiative (WHI), which found that women who took aspirin or ibuprofen at least twice a week for 5 years or more had a reduced risk of breast cancer. “The data are strong for colon cancer and reasonably strong for breast cancer,” he said.

That sentiment, though, is not universal.

“It would be premature to recommend that people start taking aspirin specifically to prevent cancer,” said Dr. Eric Jacobs, strategic director of pharmacoepidemiology for the American Cancer Society, in an e-mail. Potential side effects have to be taken into consideration, he continued, noting that even low dosages of aspirin “can substantially increase the risk of serious gastrointestinal bleeding.”

Reasons for Caution

Targeting Colorectal Precancers

The strongest data supporting the use of NSAIDs to reduce cancer risk is in colorectal cancer. One phase III trial on the horizon will assess whether an NSAID called sulindac, in combination with an investigational drug called DFMO, prevents the recurrence of colon polyps (which can eventually progress to become colorectal tumors) in patients who have previously had polyps removed.

The upcoming trial, according to Dr. Umar, follows from the very strong results seen in an earlier phase III trial in which participants who received the sulindac/DFMO combination had marked reductions in the return of colorectal polyps compared with patients who received a placebo. For advanced adenomas, which are most likely to progress to malignant colorectal tumors, the reduction was 95 percent.

This new trial will be larger than the previous trial and will examine the effects of sulindac and DFMO separately as well as in combination, Dr. Umar explained, with a primary endpoint of reduction in advanced adenomas. If the results are similar to the earlier trial, he added, they would form the basis for a submission to the FDA for approval of the drug combination to prevent advanced adenomas.

Much of the hesitation, explained Dr. Asad Umar of NCI’s Division of Cancer Prevention, stems from the lack of data from appropriately designed randomized clinical trials focused specifically on a cancer outcome. “Only when you do a randomized clinical trial do you get the complete picture of what’s going on,” he said, including potential benefits and harms.

Dr. Umar cited the experience with a different NSAID, the COX-2 inhibitor celecoxib (Celebrex). Celecoxib is approved by the FDA as an adjunct to surgery to prevent polyp formation in people with a disorder called familial adenomatous polyposis (FAP) that puts them at an increased risk for colorectal cancer. Early, smaller clinical trials to test whether daily use of celecoxib could prevent the return of colon polyps in people without FAP didn’t reveal any meaningful side effects from the drug, and did show significant reductions in polyp formation and growth. It was only in much larger trials, including the NCI-funded Adenoma Prevention with Celecoxib trial—which assessed effects of using the drug daily for 3 years—that evidence emerged for potential adverse cardiovascular effects of regular, long-term treatment with celecoxib.

The trials included in The Lancet meta-analysis, Dr. Rothwell noted, had more fatal bleeding events among participants who took a placebo than among those who took aspirin (60 versus 40). The analysis also showed a more than 8 percent reduction in all-cause mortality among aspirin users by the end of the trials included in the analysis, “nearly all of which was due to the reduction in cancer deaths,” he said.

Despite the promising data from these studies, Dr. John Baron of the University of North Carolina said he is not yet ready to endorse aspirin’s widespread use for cancer prevention. “We need to consider all of the benefits and harms that can accrue from aspirin use in various population groups,” he said. “We don’t quite have that yet.”

Filling in the Blanks

In a consensus statement published last year, an international group of researchers reviewed the published data on aspirin’s effects on cancer incidence and mortality and laid out what they determined to be the most important clinical questions that still need to be answered. These questions included how long people should take aspirin for the optimum effect, the age when they should start taking it, and the best dose, among others.

Dr. Baron, a statement co-author, admitted that it will be difficult to answer these questions. “The most important issue that needs to be dealt with immediately is the dose issue,” he said.

Opinions on dose vary. A daily low-dose aspirin (such as 81 mg) is likely to be the proper choice, Dr. Rothwell said. But Dr. Harris suggested that a higher dose, up to 325 mg at least twice a week, would also be effective.

In The Lancet meta-analysis, the risk of dying from cancer decreased regardless of the aspirin dose. But observational data from a recent Harvard study showed that, at least in people already treated for colorectal cancer, the extent of the risk reduction seemed to increase with dose. “That certainly needs to be considered,” Dr. Baron said, “because side effects from aspirin also increase with dose, although not strikingly.”

Typically, clinical trials could help to provide more definitive information on dose. But large cancer prevention trials of aspirin are very difficult to conduct, Dr. Umar acknowledged. A trial using cancer mortality as an endpoint would require a very long study with a large number of participants to demonstrate any effect. And many people are already taking aspirin for cardiac prevention and pain relief, Dr. Harris said, so gathering enough participants who don’t take aspirin for the sake of comparison would also pose a difficulty.

As far as clinical trials are concerned, Dr. Umar said, “We need to develop carefully designed studies, identify high-risk groups and surrogate endpoints, and get a genomic signature of response in addition to clinical endpoints.”

Several trials focused on high-risk groups are planned or ongoing. (See the sidebar.) In the United Kingdom, for example, participants are being enrolled in the phase III AspECT trial, which will test whether aspirin in combination with a drug that prevents and treats acid reflux (and may prevent or limit gastrointestinal bleeding) can reduce the risk of esophageal cancer in people with Barrett esophagus, which can be a precursor to the cancer.

Dr. Rothwell predicts that the findings from these trials and other studies will “firm up the evidence” in support of aspirin for cancer prevention.

In the meantime, Dr. Jacobs advised, the average person needs to proceed with an abundance of caution. “Decisions about aspirin use should be made by balancing the risks against the benefits,” he said, “so any decision about daily aspirin use should be made only in consultation with your health care professional.”

Carmen Phillips


Seeking Better Treatments for Brain Tumors in Children

Imaging study of a 6-year-old girl with medulloblastoma Imaging study of a 6-year-old girl with medulloblastoma [Click to Expand]

Minimizing the harmful side effects from cancer treatments is always important, and particularly so when treating brain tumors in children. Doctors can cure most cases of medulloblastoma, the most common malignant brain tumor in children, but radiation and chemotherapy can cause cognitive deficits in young survivors and lead to health problems later in life.

To find new treatments and to improve the care of all patients, researchers are using DNA sequencing and other new approaches to characterize tumors. The goals are to better classify patients according to the underlying biology of their tumors and to develop new treatments based on this information.

“As clinicians, we’re all trying to come up with smarter ways to treat patients with medulloblastoma, both because we just can’t cure some patients and because therapy can be hard on developing brains,” said Dr. Will Parsons of Texas Children’s Cancer Center and Baylor College of Medicine, who was the first author of a genetic study of medulloblastoma published last month in Science.

That report and two others, also published last month, provided insights into the genetic and cellular origins of the disease. The study published in Science surveyed the “genetic landscape” of medulloblastoma, while the other reports (here and here) described the molecular subtypes of the disease and introduced new tools for studying these tumors. 

“These three studies are at the forefront of a large body of genomics-based research that, in the next few years, will redefine how medulloblastoma is diagnosed and how new treatments for patients with medulloblastoma are developed,” said Dr. Malcolm Smith of NCI’s Cancer Therapy Evaluation Program (CTEP), who was not involved in the research.

Doctors have long known that medulloblastoma is a heterogeneous disease. Some tumors are cured relatively easily, whereas others, particularly those that represent recurrences, resist treatment. The reasons for this variation are not fully understood, but genetic studies have suggested that medulloblastoma consists of at least four subtypes, each with distinct genetic and clinical features.

Profiling a Pediatric Tumor

“If we could figure out which kids we could safely give less therapy to without affecting their outcomes, that would be a really important step,” said Dr. Parsons. “When we give radiation to children who are 2 or 3 or 4 years old, it can potentially cause significant health problems.”

In the genetic study, Dr. Victor Velculescu of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and his colleagues surveyed the genetic alterations and changes in the number of gene copies in 22 tumors from patients with medulloblastoma. The researchers used similar methods as in their previous genetic studies of adult cancers, including breast, colon, and glioblastoma, the most common brain tumor in adults. (Last week, the team published a report that profiled pancreatic neuroendocrine tumors.)

Perhaps the study’s most striking result was that fewer genetic mutations were found in this childhood cancer than have been found in adult cancers. On average, medulloblastoma tumors had 11 genetic mutations, of which one or more may play a role in cancer, compared with between 50 and 100 mutations in the adult cancers studied to date, the researchers reported.

“We think that a smaller number of genetic alterations is likely to be a general feature of all pediatric cancers,” said Dr. Velculescu. In theory, he continued, having fewer mutations in tumors could help investigators focus on the critical changes in the disease by narrowing the set of possible alterations.

Epigenetic Changes in Cancer

The genetic study, which NCI funded, confirmed the presence and general frequency of previously known mutations in medulloblastoma, such as those in the Wnt and hedgehog signaling pathways. But the researchers also discovered that some tumors harbored previously unknown mutations in the genes MLL2 and MLL3. These genes are involved in histone methylation, an epigenetic process that affects the structure of chromatin and the regulation of other genes.

Although the role of these mutations in medulloblastoma is not yet known, the discovery follows recent reports in other cancers of mutations in genes that are associated with epigenetic processes. “The new findings, when considered with other recent studies, suggest that epigenetic modifications are going to be an important pathway in cancer,” said Dr. Daniela Gerhard, who directs NCI’s Office of Cancer Genomics and is a co-author of the Science study.

“But the data are just coming in, so we need to determine the importance of these changes,” she continued. It is not known, for instance, whether epigenetic changes are a driver of the disease, or whether these changes are important in the survival of tumors. Dr. Gerhard also cautioned that the study was merely a first look at the genome, and “there are still quite a lot of genetic alterations to be discovered in medulloblastoma.”

Four Distinct Subtypes

In the second study, Dr. Michael Taylor of the Hospital for Sick Children, in Toronto, and his colleagues identified four distinct subgroups of medulloblastoma based on an analysis of gene expression and DNA copy number changes in more than 100 tumors. The subgroups included patients who had distinct demographics, clinical presentations, and outcomes, and whose tumors had distinct genetic signatures and abnormalities. The findings appeared in the Journal of Clinical Oncology (JCO).

Dr. Smith noted that the subtypes identified in the JCO study are supported by results from other researchers. Because the subtypes were associated with distinct patient outcomes, he continued, doctors could potentially use the subtypes in the future to help guide decisions about treatment. For instance, patients with a particularly aggressive subtype could receive more therapy, and patients who are likely to respond to initial therapy could be spared unnecessary treatment.

Unexpected Cellular Origins

The third study identified a different cell of origin for one of the medulloblastoma subtypes. Previous studies have suggested that medulloblastoma tumors originate in the cerebellum, where the tumors are located. But Dr. Richard Gilbertson of the St. Jude Children’s Research Hospital and his colleagues found that tumors associated with changes in the Wnt pathway arise from the dorsal brainstem rather than the cerebellum.

“We had a hypothesis that the cell of origin might be different, but the fact that the cell of origin wasn’t even in the cerebellum was remarkable,” Dr. Gilbertson said. The findings, he noted, “truly show that [different] subtypes of medulloblastoma are intrinsically different diseases.”

Writing in Nature, the researchers concluded that different treatments will be required for these diseases. As part of the study, the team developed mouse models that can be used to further investigate the biology of these tumors. 

Testing a Targeted Therapy

Insights into the biology of medulloblastoma tumors have already led to a clinical trial testing a targeted therapy in this disease. An experimental drug called GDC-0449, which inhibits the hedgehog signaling pathway, is being evaluated in children with recurrent medulloblastoma. Last summer, researchers reported that the drug was safe and well tolerated in a phase I trial involving about a dozen young patients.

“Right now, there is hope and excitement that we may have new therapies to introduce for these patients,” said Dr. Amar Gajjar of St. Jude, who is leading ongoing NCI-sponsored trials with the drug on behalf of the Pediatric Brain Tumor Consortium.

Meanwhile, the studies published to date suggest that patients in the Wnt subgroup tend to have very good outcomes, he noted. “So the clinical way forward for these patients is to see if we can judiciously cut back on chemotherapy and still maintain good outcomes.”

Since medulloblastoma was first described, in 1925, a tremendous amount has been learned about the biology of these tumors. Doctors can cure three out of four patients with this cancer, which was once uniformly fatal. The main challenge now, several researchers said, will be to improve on the existing survival rates while minimizing the side effects from treatment.

And, as Dr. Taylor and his colleagues noted in the conclusion of their report, researchers can now explore the idea of whether the molecular variants found in each subtype of medulloblastoma may in fact “constitute four distinct diseases.”

Edward R. Winstead

Featured Clinical Trial

Dose-Adjusted Chemotherapy for Untreated c-MYC-Positive Lymphomas

Name of the Trial
Phase II Study of Dose-Adjusted EPOCH-Rituximab in Adults with Untreated Burkitt Lymphoma and c-MYC+ Diffuse Large B-Cell Lymphoma (NCI-10-C-0052). See the protocol summary.

Dr. Keiron Dunleavy Dr. Keiron Dunleavy

Principal Investigator
Dr. Kieron Dunleavy, NCI Center for Cancer Research

Why This Trial Is Important
Burkitt lymphoma is an aggressive type of non-Hodgkin lymphoma (NHL) that often affects children and young adults. People infected with HIV are much more likely to develop Burkitt lymphoma than those who are HIV negative. A defining feature of this cancer is a chromosome change that causes increased expression of a gene called c-MYC, which encodes a protein that helps turn other genes on and off. The c-MYC gene is also abnormally active in some patients with diffuse large B-cell lymphoma (DLBCL), the most common type of NHL. Overexpression of c-MYC (known as c-MYC positivity) in these cancers is associated with a very high rate of cell proliferation.

Burkitt lymphoma can be successfully treated with a complex regimen of chemotherapy, but this treatment is often associated with a high rate of complications, especially among older patients and patients whose immune system is suppressed. In addition, patients with c-MYC-positive DLBCL tend to fare poorly with standard treatment compared with those who have c-MYC-negative disease. A chemotherapy regimen developed at NCI called EPOCH in combination with an antibody called rituximab (the EPOCH-R regimen) has been shown to help improve the outcomes of patients with some forms of aggressive NHL.

EPOCH-R appears to be particularly active against B-cell lymphomas that have high cell proliferation rates, so NCI researchers conducted a study of this regimen, with the doses of some of the drugs adjusted in each treatment cycle to achieve optimum concentrations (dose-adjusted EPOCH-R), in patients with previously untreated Burkitt lymphoma. All 30 patients in the study experienced complete remission. Now, the researchers are conducting a larger study of this treatment for patients with untreated Burkitt lymphoma to confirm the earlier results, and are extending the treatment to patients with c-MYC-positive DLBCL to see if those patients will also benefit from dose-adjusted EPOCH-R therapy.

In this trial, adult patients with newly diagnosed Burkitt lymphoma or c-MYC-positive DLBCL will be separated into low-risk and high-risk groups depending on their clinical characteristics and prognostic factors. Those in the low-risk group will be treated with at least three cycles of chemotherapy, while those in the high-risk group will receive six cycles. Patients with c-MYC-positive plasmablastic lymphoma (a very rare subtype of DLBCL characterized by the absence of CD20, the protein targeted by rituximab) will be treated with dose-adjusted EPOCH but not rituximab. Doctors will assess the safety and effectiveness of dose-adjusted EPOCH or EPOCH-R in these patients.

“We initiated this study for a couple of reasons,” said Dr. Dunleavy. “Firstly, moving on from our previous experience using dose-adjusted EPOCH-R in Burkitt lymphoma, we wanted to stratify patients into low-risk and high-risk groups and minimize the number of treatment cycles for patients with low-risk disease. Secondly, we wanted to investigate this therapeutic strategy in a multicenter study, and, thirdly, given the fact that c-MYC-positive diffuse large B-cell lymphoma has a poor outcome with standard therapy, we wanted to prospectively evaluate this therapy in that group of patients.”

For More Information
See the lists of eligibility criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.

An archive of "Featured Clinical Trial" columns is available at

Community Update

NCI Director Provides Update on New Programs and Initiatives

NCI Director Dr. Harold Varmus addresses staff at the NCI town hall meeting. NCI Director Dr. Harold Varmus addresses staff at the NCI town hall meeting held January 10.

During a January 10 town hall meeting with NCI staff, NCI Director Dr. Harold Varmus outlined priority areas for NCI investment and provided a status report on some of the initiatives and changes he announced last July during his first town hall meeting as NCI director.

Progress against cancer has been and will continue to be made, he said, citing for example the results of the National Lung Screening Trial (NLST), which will help guide screening for lung cancer in those at increased risk of getting the disease, and the promising results from recent clinical trials of targeted therapies in advanced melanoma and lung cancer. (See the related Bulletin articles here and here.)

“There are a lot of reasons for hope,” Dr. Varmus said. In the United States, he pointed out, incidence and mortality rates for many cancers are declining. “We’ve shown that science helps to reduce the burden of cancer in this country and can do so in others.”

Moving forward, three areas will have priority for funding, he said. The first: awarding roughly the same number of new research project grants in 2011 as were awarded in 2010 (approximately 1,250), with priority given to young and first-time investigators.

“I view new [research] grants, especially grants to new investigators, as the single best means to pursue new ideas,” he said. “That’s something we simply must do.”

Maintaining robust funding for genomics-based research and instituting changes to the clinical trials system are also high priorities. Genomics, Dr. Varmus said, “is delivering discoveries for much of what we’re trying to do” in all areas of cancer research and patient care, so it’s important “to ensure that the cancer genomics machines are full of fuel for the foreseeable future.”

With regard to clinical trials, many changes are already taking place, including the initial stages of reducing the number of adult clinical trials cooperative groups from nine to no more than four groups. Other changes are in the works, he continued, such as increasing reimbursement to clinicians for participating in phase II and phase III clinical trials.

Fully funding these priorities will be particularly challenging in the current economic environment, he acknowledged. “We are facing very, very difficult times,” he said.

Soliciting Feedback on Provocative Questions in Cancer Research

Last week, NCI launched the Provocative Questions Web site to engage the cancer research community in this important initiative. The project is intended to assemble a list of novel questions that will help guide NCI and its scientific communities in efforts to control cancer through laboratory, clinical, and population sciences. The Web site allows individuals to submit questions, rank questions submitted by others, and participate in an online discussion of the initiative.

Provocative Questions are inquiries that address important problems and paradoxes in cancer research considered to have received insufficient attention, for a variety of reasons. Some may be built on older, neglected observations that have never been adequately explored; some on more recent findings that are perplexing; and some on problems that were traditionally thought to be intractable but that now might be vulnerable to attack with new methods. The questions are not intended to represent the full range of important questions that NCI and its constituencies should be studying, but they should draw attention to significant underappreciated opportunities for advancing the understanding of cancer and developing new prospects for controlling it.

Because the previous Congress failed to pass a budget for 2011, government agencies are operating under a continuing resolution that is keeping the government funded at 2010 budget levels until March 4. Although appropriations committees in the House and Senate in the previous Congress approved budgets with small increases for NIH in 2011, any hope of an increase actually being enacted this year is “vanishing,” Dr. Varmus said, and decreases could be on the horizon.

The situation is particularly troublesome, he continued, because much of NCI’s budget consists of money that is already committed to research grants, cancer center grants, contracts, staff salaries, and other costs. A flat or decreased budget will make it hard to meet both existing obligations and support new research grants and programs, meaning funding to cover such shortfalls may have to come from cuts to existing NCI programs, including potentially small reductions in cancer center core grants.

As for other changes that are under way, they include the process of searching for leaders of two new programs that were announced during his first town hall meeting: the NCI Center for Cancer Genomics and the Center for Global Health.

The Center for Cancer Genomics will “amalgamate the activities we’re undertaking in cancer genomics,” including The Cancer Genome Atlas, he said. And the response from the cancer community and other organizations to the formation of the Center for Global Health—which will coordinate and prioritize NCI’s research efforts that can have a direct impact on global cancer health, primarily in poorer countries—has been especially strong. “I think everyone recognizes that it’s time to put cancer on the marquee for global health,” Dr. Varmus said.

A new associate director for cancer prevention will also join the NCI Office of the Director, and some components of NCI’s tobacco control research portfolio will likely transition to a new NIH institute devoted to research related to substance use, abuse, and addiction. That new institute will be formed primarily by combining the National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, a change that was recommended by the NIH Scientific Management Review Board. The component of NCI’s tobacco control portfolio that will shift to the new institute, he explained, will consist primarily of research into the neuroscience of addiction.

Increased collaboration with other government health agencies and cancer organizations will be critical moving forward, Dr. Varmus stressed. “In these conditions of strained budgets,” he said, “it will be important to keep our eye on the totality of the enterprise and not simply think about the NCI as the only place where cancer research occurs.”

Carmen Phillips

FDA Update

FDA Updates Safety Review of Diabetes Drug for Possible Cancer Risk

Earlier this month, the FDA said there was "inconclusive" evidence to suggest that the common diabetes drug glargine (Lantus) increases cancer risk. This was an update to a safety review the agency initiated in July 2009, after results from four observational studies suggested that users of the drug, a modified form of human insulin, had an increased cancer risk. The FDA noted that firm conclusions about the association cannot be reached at this time, “due to limitations in how the studies were designed and carried out and in the data available for analysis.”

The studies were all published online September 2009 in the journal Diabetologia; none was conducted in the United States. The FDA noted that three of the four studies showed an association between glargine use and cancer risk.

In addition, the FDA reviewed data from a randomized clinical trial of glargine in patients with type 2 diabetes and found no evidence of increased cancer risk. “However, the study was not designed or powered to evaluate cancer outcomes and these outcomes were not verified in medical records or reviewed by cancer experts,” the agency noted.

The safety review is ongoing and also includes an ongoing clinical trial called ORIGIN. An interim analysis of that trial suggested no increased risk of cancer associated with glargine, the agency explained.


In Memoriam: Arthur Schatzkin, Branch Chief in DCEG

Dr. Arthur Schatzkin Dr. Arthur Schatzkin

Dr. Arthur Schatzkin, chief of the Nutritional Epidemiology Branch (NEB) in NCI’s Division of Cancer Epidemiology and Genetics (DCEG), passed away on January 20 from cancer. Dr. Schatzkin was an internationally renowned pioneer in the field of nutrition and cancer who joined NCI in 1984.

Dr. Schatzkin was committed to understanding the role of nutrition in cancer etiology and prevention. Early in his career, he was the first to describe an association between moderate alcohol intake and breast cancer risk. He then turned his attention to the role of diet in preventing colorectal cancer. Dr. Schatzkin led the landmark NCI Polyp Prevention Trial, a 4-year randomized trial that showed that, contrary to the prevailing hypothesis, a low-fat, high-fiber diet has no effect on adenoma recurrence.

Dr. Schatzkin addressed major issues in nutritional epidemiology, including two major methodologic limitations: the limited range of reported dietary intake in cohort studies, and the measurement error associated with self-reported dietary assessment. To address the first issue, he launched the NIH-AARP Diet and Health Study, which was at the time the largest-ever prospective cohort study. Research from this long-term investigation of approximately 500,000 men and women has produced more than 100 original scientific papers, and it is a prized resource for investigators worldwide. To address the complex issue of dietary measurement error, Dr. Schatzkin played a key role in the Observing Protein and Energy Nutrition (OPEN) biomarker study. He also supported the development of new Web-based methods to measure diet, physical activity, and energy balance. The author of more than 300 original research articles, he participated on an international expert panel convened in 2007 by the World Cancer Research Fund and the American Institute for Cancer Research to report on the current evidence regarding food, nutrition, physical activity, and cancer.

Throughout his career, Dr. Schatzkin was dedicated to the advancement of nutritional epidemiology and the mentoring of young scientists. During his 11 years as branch chief, the NEB grew from two investigators to a large and successful team of more than 20 scientists.

“Arthur had great personal warmth and humor, tremendous intellectual curiosity and honesty, a genuine interest in all, and a passion for improving public health through exemplary science,” said Dr. Joseph F. Fraumeni, Jr., director of DCEG. “He will be deeply missed.”

Dr. Schatzkin is survived by his wife, Dr. Tamara Harris, who is chief of the Geriatric Epidemiology Section at the National Institute on Aging, and their children, Rebecca and Eric.

New Program Aims to Help Businesses Navigate Regulatory Clearance for Products

The NCI Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Programs announced the launch of a new pilot Regulatory Assistance Program. This first-ever NCI SBIR Regulatory Assistance Program is designed to aid NCI SBIR and STTR phase II awardees in understanding and managing the regulatory requirements for advancing their products to the marketplace. The program is part of NCI’s latest efforts to go beyond funding support to help small businesses bring innovative cancer products to market. This competitive program is open to NCI phase II grantees and contractors with projects that are current or have ended within the last 2 years.

Applications will be accepted and reviewed on an ongoing basis until 5:00 pm EST, February 4. Final selection of participants will be made by March 4.

Once selected, the awardees will be matched with experienced regulatory consultants in the areas of therapeutic and device development who will assist them in creating a comprehensive regulatory plan aimed at optimizing their company’s movement through the FDA approval process.

More information about the new Regulatory Assistance Program and how to apply is available online.

New Issue of CCR Connections Published

Cover of CCR Connections

The newest issue of NCI’s Center for Cancer Research (CCR) news magazine, CCR Connections, is available online. Volume 4, number 2, features articles about partnerships between CCR staff members and scientists in other countries, including a profile of the Princess of Thailand, herself a research scientist and CCR collaborator.

This issue also includes a story about Dr. Stephen Rosenberg’s work with National Human Genome Research Institute scientist Dr. Yardena Samuels to understand the genetics of melanoma; a story about research by Dr. Ira Pastan and Dr. Michael Gottesman that broke research ground on the molecular basis of chemoresistance; and an introduction to Dr. Alan Wayne and his 11-year-old patient Avery Lachapelle, who has been battling recurrent acute lymphoblastic leukemia since he was 14 months old.

CCR Connections is published semiannually. Please send requests for print or online subscriptions to

State Cancer Legislative Database Adds Obesity Prevention

NCI’s State Cancer Legislative Database (SCLD), a program that maintains a database of state cancer-related health policies, recently added obesity prevention to the list of covered topics. Information on topics is continually updated and made available quarterly, so content will be added to the obesity prevention topic in the coming months.

The current issue of the SCLD Update introduces the obesity prevention topic and, along with it, subtopics on food and nutrition awareness, competitive foods, food environment, nutrition education, reimbursable meals, research, and state capacity. The topic area is expected to expand to include new subject matter that focuses on energy expenditure, including requirements for physical activity and physical education during the school day. The Legislative Data Byte in the current SCLD Update highlights states with obesity laws incorporating horizontal governance, an approach to policy development that involves collaboration and shared responsibility among government entities.