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February 9, 2010 • Volume 7 / Number 3

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Chromosomes inside the silhouette of a person depicting personalized medicineMelanoma Drugs Have Unintended Effects in Some Tumors

Some patients with advanced melanoma have had dramatic responses to a new class of targeted drugs in early stage clinical trials. While the long-term effects of these drugs, called BRAF inhibitors, are not yet known, two reports suggest that these drugs may have unintended consequences in patients whose tumors lack mutations in the BRAF gene. Read more > >


Dr. Lenora JohnsonGuest Director's Update: Join the Evolution

by Dr. Lenora Johnson

We all know the cliché, but it's true nevertheless: We live in a small world, one that seems to get smaller with each new technological advance. Almost immediately after the tragic earthquake in Haiti, for instance, smart phones, Twitter feeds, and blogs were literally buzzing with the news, and almost as quickly people responded with aid, often using these same communication tools. Even now, in the midst of record snow storms blanketing the nation's capital, NCI's ability to communicate vital information is hardly affected. Read more > >




  • FDA Update

    • Another Use for the Cancer Drug Lapatinib

    NIH Update

    • NIH Clinical Center to Track Radiation Doses from Diagnostic Imaging Update

    • Online Course for Health Professionals on Clinical Trials


    • NCI's Dr. Robert Wiltrout Named FLC's Lab Director of the Year
    • Learn about NCI's Cancer Biobank at caHUB Public Information Meetings
    • NCI Symposium Will Look at Translational Genomics
    • World Cancer Day Observed on February 4
    • NCI and AACC Partner to Bridge Gap between Lab and Clinic

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

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.

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Featured Article

Melanoma Drugs Have Unintended Effects in Some Tumors

Chromosomes inside the silhouette of a person depicting personalized medicine

Some patients with advanced melanoma have had dramatic responses to a new class of targeted drugs in early stage clinical trials. While the long-term effects of these drugs, called BRAF inhibitors, are not yet known, two reports suggest that these drugs may have unintended consequences in patients whose tumors lack mutations in the BRAF gene.

In separate studies, scientists in Great Britain and the United States tested the drugs in the laboratory to better understand how BRAF inhibitors behave in cells. To their surprise, the drugs actually spurred the growth of some tumors. The preliminary findings raise the possibility that certain patients should not receive BRAF inhibitors because the drugs could make their cancers worse.

Based on these studies, there is reason to suspect that giving these drugs to patients whose tumors have normal copies of the BRAF gene could actually accelerate tumor growth, said Dr. Paul Chapman of Memorial Sloan-Kettering Cancer Center, who has led clinical trials of BRAF inhibitors but was not involved in these studies. “The findings suggest that we need to avoid treating patients who do not have certain genetic mutations because you could potentially do harm,” he added.

The drugs primarily target a mutation in the BRAF gene called V600E. Many but not all of the patients enrolled in clinical trials of BRAF inhibitors have had this mutation in their tumors. The alteration is present in approximately half of all melanomas, and it activates growth-promoting messages from the MAPK signaling pathway.

The new studies focused on tumors that had mutations elsewhere in the pathway. “Both groups found that BRAF inhibitors can promote tumor growth in melanoma cells that lack the V600E mutation by activating other elements of the pathway,” said Dr. Shiva Malek of Genentech, who led one of the studies.

Reporting their findings online in Nature on February 3, the researchers proposed several models that could potentially explain how a drug designed to inhibit the pathway could lead to its activation.

“Our results are certainly paradoxical,” said the study’s first author, Dr. Georgia Hatzivassiliou of Genentech. “You expect an inhibitor to be an inhibitor under any circumstance.” But she noted that the new results clearly indicate that the effects of BRAF inhibitors depend on the cellular context, or the genetic background of a tumor cell.

Both groups found, for instance, that the drugs could activate BRAF signaling in melanoma tumors with mutations in the RAS gene, which is part of the BRAF pathway. As the British researchers reported in the January 22 Cell, the drugs fueled rather than blocked the growth of melanoma cells with RAS mutations.

The study’s lead investigator, Dr. Richard Marais of the Institute of Cancer Research in the United Kingdom, said in a statement that the new findings would give researchers insights into how BRAF drugs will behave in humans. Both studies, for instance, concluded that a central player in the activation of the BRAF pathway was a protein called CRAF, which is a close relative of BRAF.

“The findings provide a framework for understanding possible mechanisms of resistance to BRAF inhibitors,” said Dr. Chapman. “The results give researchers an idea where to look in the signaling pathway.”

Dr. Neal Rosen, also at Memorial Sloan-Kettering, published a study last year describing some of the complexities of the BRAF pathway. He and others have been investigating the genetic alterations that confer resistance to these drugs, but progress has been slow because it has been difficult to obtain enough tumor samples from patients with melanoma who developed resistance to BRAF inhibitors, noted Dr. Chapman.

That could eventually change as new clinical trials of BRAF inhibitors move forward, including a phase III study that is expected to open soon. 

“The bottom line for patients is that we’ve made great strides in developing drugs to target this pathway,” said Dr. Malek. “But we can always do better. Every tumor is different, and understanding more about the biology of these tumors will allow us to develop smarter interventions.”

—Edward R. Winstead

Cancer Research Highlights

Symptoms of Ovarian Cancer May Not Help Early Detection

Some women with ovarian cancer report symptoms before diagnosis, including abdominal pain, bloating, and feeling full. But a new study concludes that monitoring women for these relatively nonspecific symptoms would be of limited value in detecting the disease. Doctors would have to evaluate 100 women with these symptoms to find one ovarian cancer, the researchers reported online in the Journal of the National Cancer Institute on January 28.

These findings come nearly 3 years after a consensus statement issued by three U.S. medical organizations advised women who experience certain symptoms over a period of time to consider talking with their physicians. Recognizing symptoms reported by women who develop ovarian cancer could assist with diagnosis, the statement said.

In the new study, Dr. Mary Anne Rossing of the Fred Hutchinson Cancer Research Center and her colleagues interviewed 812 patients with ovarian cancer and 1,300 women without the disease about their symptoms. In most cases, symptoms appeared less than 6 months before a diagnosis.

“We would all like to find a perfect way to detect ovarian cancer in its early stages,” said Dr. Rossing. “Knowing, however, that the symptoms are fairly nonspecific and that ovarian cancer is relatively rare in the general population, it’s not surprising that these symptoms would have a low ability to predict the disease in the general population.”

The findings “highlight the urgent need to develop better molecular markers and improved imaging modalities for ovarian cancer screening,” noted Drs. Ilana Cass and Beth Karlan of Cedars-Sinai Medical Center in an accompanying editorial.

Trastuzumab Benefits Women with Locally Advanced, Inflammatory Breast Cancer

Findings from an international clinical trial suggest a new treatment option for some women with aggressive types of breast cancer. In the trial, women treated with trastuzumab (Herceptin) and chemotherapy before surgery (neoadjuvant) and trastuzumab again after surgery (adjuvant) had a reduced risk of the disease recurring or progressing after 3 years compared with women who received pre-surgical chemotherapy but no trastuzumab. The findings were published in the January 30 Lancet.

The 230 women enrolled in the trial had either locally advanced or inflammatory breast cancer that was HER2-positive. Although trastuzumab has been shown to improve overall survival in women with HER2-positive early stage and metastatic breast cancer, the drug has not been closely studied in women with these intermediate stages of breast cancer, the research team wrote.

Patients who were randomly assigned to receive trastuzumab took the drug for a total of 1 year. Three-year event-free survival—with an event defined as disease recurrence, progression, or death from any cause—was 71 percent in patients treated with trastuzumab and 56 percent in those who did not receive it. The pathologic complete response rate, or no detectable presence of cancer, was nearly doubled among the women who received trastuzumab.

To date, there is no statistically significant improvement in overall survival among the women who received trastuzumab. This could be due to the fact that 17 percent of the women in the chemotherapy-alone arm also received adjuvant trastuzumab, while some other patients received the drug following a recurrence, explained the trial’s principal investigator, Dr. Luca Gianni of the Italian National Cancer Institute, in a Lancet podcast.

There were no significant issues with cardiac side effects, which have been a recurring problem in other breast cancer trials involving trastuzumab and doxorubicin, a drug that was part of the chemotherapy regimen used in the trial.

According to Dr. Massimo Cristofanilli, chair of the Department of Medical Oncology at Fox Chase Cancer Center, pathologic complete response “is the most important prognostic factor” in women with these breast cancer types. The low rates of cardiac side effects, he noted, were likely due to the fact that patients in the trial had not been pretreated, had optimal heart function, and the cumulative doses of doxorubicin were below those typically associated with cardiotoxicity.

Tumor-targeting Antibodies Against Glycoproteins May Be Markers of Early Cancer

In a proof-of-concept study, researchers from the NCI-funded Alliance of Glycobiologists for Detection of Cancer and Cancer Risk showed that autoantibodies targeting abnormal glycoproteins (proteins with sugar molecules attached) produced by tumors may serve as biomarkers for cancer detection. Autoantibodies are antibodies directed against the body’s own tissues, including tumor cells. The findings were published February 2 in Cancer Research. The work was coordinated by Dr. Karl Krueger of the Cancer Biomarkers Research Group (CBRG) in NCI’s Division of Cancer Prevention.

Because the sugars that are attached to certain glycoproteins, called O-glycoproteins, on the surface of cancer cells have been found to be abnormal, researchers led by Dr. Hans H. Wandall of the University of Copenhagen synthesized a large number of abnormally glycosylated peptides (protein fragments) and used them to make a microarray for detecting autoantibodies against abnormal O-glycoproteins. Glycosylation is the process of adding sugar molecules to proteins, lipids (fats), or other biological molecules.

The researchers tested the microarray using blood samples from 20 breast cancer patients who were enrolled in a clinical trial of an anticancer vaccine targeting O-glycoproteins. The researchers knew from previous analyses that many of the patients had developed immunoglobulin G antibodies against several O-glycoproteins, and these autoantibodies were indeed detected by the new microarray.

The researchers then used the microarray to scan blood samples from 58 patients with newly diagnosed breast, ovarian, or prostate cancer and from 39 age- and sex-matched healthy control subjects.

Autoantibodies to several of the O-glycoproteins on the microarray were found in 5 out of 26 breast cancer patients, 5 out of 20 ovarian cancer patients, and 4 out of 10 prostate cancer patients. No autoantibodies to any of the O-glycoproteins were found in the healthy control subjects.

“Thanks to emerging technologies such as the one used in this study, scientists have identified biomarkers based on the carbohydrate (sugar) portion of a glycoprotein that may be novel targets for the early detection and diagnosis of certain cancers,” said Dr. Sudhir Srivastava, chief of the CBRG. Nevertheless, he added, additional work is needed and larger sets of specimens must be analyzed to fully define the clinical value of this approach.

Gene Mutation Linked to Poor Survival in Children with Medulloblastoma

Results from a small, retrospective study suggest that a single genetic mutation may be linked to poor survival in children with medulloblastoma, the most common type of pediatric brain tumor. In the study, released online February 8 in the Journal of Clinical Oncology, no patient with medulloblastoma whose tumor had a mutation in the TP53 gene was alive after 5 years, even though the large majority of patients were considered to be at average risk for disease progression after treatment, reported Dr. Cynthia Hawkins and colleagues from the Hospital for Sick Children in Toronto.

With modern treatment protocols, approximately 80 percent of average-risk patients with medulloblastoma—classified as such based on whether their tumor could be completely removed, their age, and whether they had metastases—survive for 5 years or more. “So we’ve identified a group of patients based on clinical factors who do well, on average, but still 20 percent of those patients are dying and we don’t know why,” Dr. Hawkins said.

The study involved 108 children treated for medulloblastoma between 1995 and 2007. Tumor samples were available for DNA sequencing from 49 of these children, and 8 had a TP53 mutation. TP53 mutations were strongly associated with early tumor recurrences. Of the 27 patients considered to be at average risk from this group of 49 children, 8 died within 5 years, 6 of whom had TP53 mutations.

Overall, 5-year survival rates for patients with TP53 mutations was 0 percent, compared with 74 percent for patients whose tumors had a normal, or wild-type, TP53 gene. Among the average-risk patients, the discrepancy for progression-free survival was greater still, 0 percent compared with 87 percent.

“All patients with TP53-mutated medulloblastomas presented with local disease and experienced recurrence locally,” the researchers wrote. “This implies that, as opposed to other molecular alterations found in medulloblastoma that are associated with dissemination, TP53 mutation causes an aggressive phenotype through other mechanisms.”

The finding of an association between TP53 status and medulloblastoma outcome is “important information,” said Dr. Javed Khan of NCI’s Pediatric Oncology Branch in the Center for Cancer Research. Dr. Khan concurred with the authors that the findings need to be validated in a larger, prospective study.

Guest Director's Update

This is the second article in a series of stories and commentaries related to cancer communications. Look for the symbol on the left in an upcoming issue for the next article in the series.

Join the Evolution

Dr. Lenora Johnson Dr. Lenora Johnson

We all know the cliché, but it’s true nevertheless: We live in a small world, one that seems to get smaller with each new technological advance. Almost immediately after the tragic earthquake in Haiti, for instance, smart phones, Twitter feeds, and blogs were literally buzzing with the news, and almost as quickly people responded with aid, often using these same communication tools. Even now, in the midst of record snow storms blanketing the nation's capital, NCI's ability to communicate vital information is hardly affected.

The hub of this interconnectivity, the Internet, is one of the greatest unifying forces of our time. According to the Pew Research Center, 74 percent of Americans age 18 and older use the Internet, and data from NCI’s Health Information National Trends Survey  show that almost 64 percent of the online population has searched the Internet for health information. Thanks to the expanding availability of Internet-ready mobile devices, the digital divide between socioeconomic groups is shrinking. At NCI, we have long recognized the immense value of the Web as a tool for accomplishing our mission of advancing cancer research and care, and we understand that its importance will only continue to grow.

Tile seeking ideas to improve

As we consider innovative ways to support the information needs of the public, we are constantly searching for new ways we can use technology to meet growing demands for instant, at-your-fingertips information. Through NCI’s Cancer Information Service, for example, not only can those seeking information receive it by calling 1-800-4-CANCER, but they can also engage with cancer information specialists via LiveHelp, online instant messaging. At NCI, we are also expanding our activity in the ever-changing world of social media, with a small but increasing presence on sites like YouTube and Twitter. Our goal is not only to provide evidence-based information, but to provide it to the right person at the right time, in the most appropriate language and format.

To that end, we are proud to announce changes to our flagship resource, NCI’s Web site We are calling it an “evolution” rather than a site redesign because it is not a one-time change; rather, we will roll out meaningful and significant enhancements in phases, and we will engage key stakeholders in the process at critical points.

A central component of this initiative is an unprecedented call to our many stakeholders—including advocates and advocacy organizations, NCI-designated cancer centers, NCI-supported programs, extramural researchers, health care professionals, and the public—to provide their thoughts on how can become a more effective communication tool.

We are looking for ideas big or small, simple or complex. It may be a two-sentence suggestion about the kind of graphics or images that are used on the site, or a thoroughly detailed concept for how we can make features such as patient and health professional cancer treatment summaries or our clinical trials search page more effective. In short, we want to know how you—both individuals and organizations—think can be enhanced to better meet the needs of our diverse audience.

Your thoughts and ideas about can be submitted through an online forum at We also encourage visitors to review the feedback that others have submitted. In addition to sharing your own suggestions, visitors to this site can make someone else’s good idea even better by your votes and comments. The dialogue will be open until March 31, 2010. After that date, a new section established on will provide updates on progress and program milestones for the site’s evolution.

NCI leaders and staff are extremely excited about this initiative. Time and again the cancer community has demonstrated its commitment to advancing cancer research and to innovative projects that aim to reduce the burden of cancer, so we are eager to see the novel and exciting ideas you propose for the next generation of

Dr. Lenora E. Johnson
Director, NCI's Office of Communications and Education

Special Report

Experts Recommend Steps to Increase Colorectal Cancer Screening in Primary Care

Enhancing Use and Quality of Colorectal Cancer Screening logo

Nearly 50,000 people die of colorectal cancer (CRC) each year in the United States, a rate second only to lung cancer deaths. Evidence shows that screening for CRC can reduce mortality and that CRC can be prevented by identifying and removing precancerous lesions known as adenomatous polyps. Guidelines recommend regular screening for adults older than age 50 who are at average risk, yet “screening is underused,” concluded an independent panel of experts at an NIH State-of-the-Science conference last week.

“We recognize that some people may find colorectal cancer screening tests to be unpleasant and time consuming,” said Dr. Donald Steinwachs of Johns Hopkins University, who chaired the 13-member panel. But “we need to find ways to encourage more people to get these important tests.”

Though CRC screening for this target group has approximately doubled in the decade ending in 2008, to about 55 percent, “millions of eligible people are not screened by any method,” the panel stressed in a draft conference statement. Many scientists at the conference believe rates in the United States should approach 80 percent, and the 13-member panel identified six strategies to achieve this goal.

“One of the strengths of CRC screening is that options are available,” said Dr. Carrie Klabunde, chair of the conference planning committee and an epidemiologist in the Health Services and Economics Branch in NCI’s Division of Cancer Control and Population Sciences. Nearly all of the recent increase in screening rates was driven by greater use of colonoscopy after Medicare began to cover the test in 2001.

Taking the Campaign to Primary Care Practices in the United States

“Many of the screening issues identified by the panel, indeed most preventive services delivered in the United States, occur within the context of the routine medical practices of primary care physicians,” said Dr. Klabunde. “And a shortage is looming, since they now comprise less than a third of U.S. physicians and their number is declining.”

Beyond CRC screening, “primary care physicians are faced with an expanding list of preventive services they are expected to deliver, yet the time to do so is woefully inadequate,” she explained. “This is why it is so important to identify effective and efficient ways to deliver the recommended CRC screening tests to eligible adults.”

Over the last 5 years, NCI has joined together with the Agency for Healthcare Research and Quality to fund research that might improve the delivery of preventive services. From a number of different projects and published studies, they applied a “New Model of Primary Care Delivery” to colorectal cancer screening. An article describing the model, published in the Journal of General Internal Medicine in 2007, outlined strategies for enhancing delivery of colorectal cancer screening in primary care, including fostering a team approach, developing relevant information systems, involving patients in decisions, monitoring the performance of the practice, enhancing reimbursement, and providing training. Many of these themes were discussed during last week’s State-of-the-Science conference.

At the conference, proponents of colonoscopy and its virtual counterpart, computed tomography (CT) colonography, promoted these two options, despite the fact that achieving high rates of screening solely with colonoscopy or CT colonography appears unlikely given the current lack of capacity and number of trained providers. Also, CT colonography is not covered by Medicare, nor is it currently recommended by the U.S. Preventive Services Task Force (USPSTF), one of two major groups that have issued guidelines on colorectal cancer screening. The USPSTF does not recommend colonoscopy over other screening options (including fecal occult blood testing (FOBT), sigmoidoscopy, and barium enema), while guidelines from the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society state that tests providing a full structural examination of the colon are preferred over other tests.

“Not only do we lack randomized, controlled trial data to warrant such a preference,” Dr. Klabunde explained, but there is evidence that other screening options that use colonoscopy as a diagnostic follow-up test can play a role in systems that achieve high screening rates. The panel heard some of this evidence from the Veterans Health Administration, Kaiser Permanente of Northern California, and the National Health Service in Great Britain at the conference. And a newer version of the FOBT, the fecal immunochemical test, has shown promise in detecting colorectal cancer while minimizing patient burden by not requiring dietary or medication restrictions prior to screening.

Each screening method may have its place, depending on patient preferences, provider capacity, and access to and availability of services; those issues are addressed by two of the panel’s six recommendations:

  • Eliminate financial barriers to colorectal cancer screening and appropriate follow up
  • Conduct research to assess the effectiveness of tailoring programs to match the characteristics and preferences of target population groups to increase colorectal cancer screening

The panel found that the most important factors associated with being screened are having insurance coverage and access to a regular health care provider. They also emphasized the need for targeted strategies for specific subgroups that have below-average screening rates. For example, Hispanics are less likely to be screened than non-Hispanic whites.

“In the United States, we really need to look more carefully at the context where most people would get screened,” said Dr. Klabunde, referring to the office practices of primary care physicians. Two of the panel’s recommendations focus on this care setting:

  • Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings
  • Widely implement interventions that have proven effective at increasing colorectal cancer screening, including patient reminder systems and one-on-one interactions with providers, educators, or navigators

The conference was sponsored by the NIH Office of Medical Applications of Research and NCI, along with other NIH and Department of Health and Human Services agencies. The independent panel included experts in the fields of cancer surveillance, health services research, community-based research, informed decision-making, access to care, health care policy, health communication, health economics, health disparities, epidemiology, statistics, thoracic radiology, internal medicine, gastroenterology, public health, end-of-life care, and a public representative.

An evidence report on enhancing the use and quality of CRC screening that was developed for the panel is available online.

Addison Greenwood

Profiles in Cancer Research

Dr. Raju Kucherlapati

Dr. Raju Kucherlapati Dr. Raju Kucherlapati

Paul C. Cabot Professor of Genetics and Professor of Medicine, Harvard Medical School Director Emeritus, Harvard Medical School-Partners HealthCare Center for Personalized Genetic Medicine
Principal Investigator, Genome Characterization Center, The Cancer Genome Atlas

Like the thousands of scientists from around the world who worked on the Human Genome Project (HGP), Dr. Raju Kucherlapati knew it would take unprecedented teamwork and determination to tackle one of history’s great scientific challenges. Fifteen years later, they had successfully mapped the genome, but their success was only a first step toward a new kind of medicine.

“Our goal now is to help physicians to better understand human disease and develop medical tools that can help match treatments to individual genetic variations,” said Dr. Kucherlapati. He was a key contributor to many of the scientific milestones that led to the Human Genome Project, a collaborating researcher while it was under way, and among the authors of the published results.


During the subsequent decade at Harvard, he has been instrumental in key initiatives as the era of personalized medicine has begun to take shape. “If you want to translate scientific knowledge into clinical practice, you’ve got to be closely affiliated with patients and a good hospital,” he explained.

He also serves as a principal investigator for The Cancer Genome Atlas (TCGA), an effort funded by NCI and the National Human Genome Research Institute that builds on the Human Genome Project to systematically characterize the genomic changes that occur in cancer. He and researchers at Harvard Medical School and Brigham and Women’s Hospital, one of TCGA’s Genome Characterization Centers, are working to characterize the genetic and genomic changes found in cancer samples. Their goal is to understand how cancer develops and to identify meaningful subtypes of cancer to help determine which drugs are most likely to work and in which patients. This research could also lead to novel therapeutic approaches.

Early Days and Compelling Colleagues

Born in India during World War II, Dr. Kucherlapati came to the United States in 1967 to attend graduate school at the University of Illinois. Very soon he became interested in the work of Dr. Frank Ruddle, a professor at Yale whose genetics laboratory was at the forefront of human gene mapping.

In exploring the possibility of a post-doctoral position in the lab, Dr. Kucherlapati decided to simply contact Dr. Ruddle directly. “I didn’t quite realize how presumptuous it might seem to just fire off a letter to Yale,” he said, but he was delighted to receive an invitation in response. “When he said, ‘Come on over!’ I packed up my Volkswagen Beetle and headed to New Haven the day after my thesis defense, before he could change his mind.”

For decades, most work on the behavior of genes was done not in mammals but in fungi and bacteria. At that time, the Ruddle lab was helping to pioneer methods to sequence human genes.

The Ruddle lab attracted interest from a number of researchers, including a geneticist from the University of Wisconsin, Dr. Oliver Smithies, a future Nobel Laureate with whom Dr. Kucherlapati began mapping the beta-2 microglobulin gene. Their relationship continued after Dr. Kucherlapati became an assistant professor of genetics at Princeton, and it eventually led to an effective way to target genes that would become a staple of genetic research, the “knockout mouse.”

Dr. Kucherlapati later played a key role in helping NCI develop the Mouse Models of Human Cancers Consortium in the 1990s. He helped newly appointed NCI Director Dr. Richard Klausner decide that significant new progress could be made if there were better model systems for studying genetics, and he would eventually be one of the authors on the 2002 paper that reported the sequencing of the mouse genome.

Decoding the Human Genome

By 1990, Dr. Kucherlapati was on the Genome Research Review Committee, providing peer review for grants to support the Human Genome Project, and would later serve on the National Advisory Council for Human Genome Research.

He was also active in the lab. The vast undertaking of the Human Genome Project was organized around the 23 pairs of human chromosomes, where the DNA base pairs are strung in long sequences, some of them composing genes. Dr. Kucherlapati received funding to work on chromosome 12 and collaborated on the project with several other prominent researchers, including Dr. Richard Gibbs, currently director of the Human Genome Sequencing Center at Baylor College of Medicine.

“The goal was always to try to bring together different people who were already doing the work,” Dr. Kucherlapati explained. “Frank [Ruddle], Sherman Weissman, and David Ward from Yale joined in, and altogether we constituted a national ‘team’ for [chromosome] 12,” he said, “first mapping and later for sequencing.” The scientists talked on the phone often in this pre-Internet era, and convened for meetings a couple of times each year. “Raju brought amazing leadership and organization to the chromosome 12 group,” said Dr. Gibbs. “He’s a valuable colleague and much appreciated collaborator.”

  “We shared everything about what we were seeing and doing. It was really the first time at the NIH that we agreed to deposit all of the data generated in our separate labs in the public database within 48 hours,” recalled Dr. Kucherlapati. “It was highly controversial. There were those who just hated it; who thought that big science is not real science or that all good science has to be done in small, individual labs. But I’ve always felt that working with other people is exciting.”

Team Science Can Be Personal

And he was very good at it, said Dr. Smithies, who cherishes their long and rewarding friendship. “Successful collaborations often make for the best of friends. We’ve worked together on a number of projects,” Dr. Smithies recalled, thinking fondly of many long weekends spent discussing science and other topics with his friend and colleague.

As their collegial relationship matured, said Dr. Smithies, it exemplified the key to successful collaboration. “You really have to think about what can benefit the other person,” he said. If everyone takes that tack, he has found that one’s own interests will automatically benefit.

The beta 2-microglobulin project took about 3 years, and Dr. Smithies said that it was their previous collaborations that made it work so effeciently. “Without some of the things I learned in our earlier work together, I wouldn’t have been able to design the experiments” that ultimately led to the 2007 Nobel Prize in Physiology or Medicine. In fact, on one of the key papers referenced in that citation, published in Nature in 1985, Dr. Kucherlapati was listed as senior author.

“When he won the Nobel, Oliver asked me to come to Stockholm,” said Dr. Kucherlapati. “It was tremendously exciting to be a part of that.”

“The collaboration with Raju,” said Dr. Smithies, “and the friendship that grew out of it, I regard as a very precious part of my scientific life.”

The list of scientists Dr. Kucherlapati has worked with is long and illustrious, and the era of human genetics his career has spanned has been historic. Far from looking back, however, he is energetically advocating for the transformation of medicine that is now becoming possible.

—Addison Greenwood

Cancer Center Profile

The University of Texas M. D. Anderson Cancer Center

President: Dr. John Mendelsohn • 1515 Holcombe Blvd., Houston, TX 77030
Phone: 1-877-MDA-6789 • Web site:


M. D. Anderson campus photo M. D. Anderson's main campus is located in Houston, TX

The University of Texas M. D. Anderson Cancer Center was established by the Texas State Legislature in 1941, and it became one of the nation’s first three federally designated comprehensive cancer centers after the passage of the National Cancer Act of 1971. Today, M. D. Anderson is recognized throughout the world for its many contributions to cancer patient care, research, education, and prevention.

M. D. Anderson is a free-standing, degree-granting component of The University of Texas System. In 2009, U.S. News & World Report’s “America’s Best Hospitals” survey ranked M. D. Anderson as the top hospital in the nation for cancer care. The Center has achieved this ranking six times in the past 8 years.

M. D. Anderson is undergoing a period of unprecedented growth. A workforce of about 17,000 includes nearly 1,500 full-time faculty and is supported by about 1,300 onsite volunteers. More than 6,000 trainees take part each year in educational programs, including advanced degrees in biomedical sciences and bachelor’s degrees in allied health disciplines.


M. D. Anderson’s strength lies in its ability to rapidly translate scientific knowledge to better cancer therapies and prevention strategies. The center currently holds 12 Specialized Programs of Research Excellence (SPORE) grants from NCI for advancing research in cancers of the bladder, brain, breast, uterus, head and neck, lung (shared with The University of Texas Southwestern Medical Center), ovaries, pancreas, and prostate, as well as leukemia, lymphoma, and melanoma.

M. D. Anderson also administers an NCI-funded Community Clinical Oncology Program (CCOP) Research Base, which prepares cancer control and prevention trials. These trials are then made available to a national network of sites so that patients can have access to state-of the-art cancer care and clinical protocols without having to relocate temporarily or leave the support of their communities.

Patient Care

Since 1944, about 800,000 patients have turned to M. D. Anderson for multidisciplinary cancer care—more than 96,000 in the last year alone. Last year M. D. Anderson had more than 1,000 active clinical trial protocols, with more than 11,000 patients who took part in trials of novel potential therapies, perhaps the largest such program in the world. Late in 2010, M. D. Anderson will begin opening an additional 12 floors atop its Alkek Hospital, adding more than 300 inpatient beds to the current complement of 500.

M. D. Anderson is accredited by the Joint Commission, a nonprofit hospital accreditation group, and holds Magnet Nursing Services Recognition status from the American Nurses Credentialing Center.

Other Notable Programs

In addition to M. D. Anderson’s main campus in Houston and two research campuses in Bastrop County, TX, the center has developed a number of local, national, and international affiliations. All are united by M. D. Anderson’s mission to eliminate cancer in Texas, the nation, and the world.

The institution is also expanding its research endeavors with the creation of the McCombs Institute for the Early Detection and Treatment of Cancer. Composed of seven centers, the McCombs Institute focuses on genomics, proteomics, screening, RNA interference and non-coding RNAs, diagnostic imaging, and drug development, and it is located adjacent to the M. D. Anderson Proton Therapy Center.

The new Duncan Family Institute for Cancer Prevention and Risk Assessment will help accelerate the transfer of discoveries in prevention and genetic and lifestyle risk factor research to clinical and community settings.

Featured Clinical Trial

Optimizing Chemotherapy with Bevacizumab for Ovarian Cancer

Name of the Trial
Phase III Randomized Study of Bevacizumab in Combination with Intravenous Versus Intraperitoneal Chemotherapy in Patients with Stage II, III, or IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Carcinoma (GOG-0252).  See the protocol summary.

Dr. Joan Walker Dr. Joan Walker

Principal Investigator
Dr. Joan Walker, Gynecologic Oncology Group

Why This Trial Is Important
Women with ovarian cancer usually undergo surgery to determine the cancer’s stage and to remove as much malignant tissue as possible. Following surgery, these women are treated with chemotherapy in an effort to eliminate remaining cancer cells.

Typically, chemotherapy for ovarian cancer is administered intravenously (IV) and travels throughout the body in the blood (systemic chemotherapy). Research by the Gynecologic Oncology Group and others, however, has demonstrated that combining IV chemotherapy with the delivery of chemotherapy drugs directly into the peritoneal cavity (intraperitoneal, or IP, chemotherapy) is more effective in delaying cancer progression and helping patients live longer. Since tumors are often confined to the peritoneal cavity in patients with ovarian cancer (as well as in those with fallopian tube or primary peritoneal cancer, which are biologically similar diseases), IP chemotherapy may allow for a greater concentration of anticancer drugs in the area around the tumors while limiting side effects elsewhere in the body. Results published in 2006 from a phase III trial showing a median increase in survival of 12 months for women treated with IV plus IP chemotherapy led NCI to issue a clinical announcement encouraging use of the combined treatment.

Other recent developments in the treatment of ovarian cancer may offer benefits similar to those seen with IV plus IP chemotherapy while avoiding some of problems associated with it (such as increased toxicity and difficulty of administration). A recent phase III study using the chemotherapy drug paclitaxel intravenously on a weekly basis, along with IV carboplatin given every 3 weeks, yielded improvements in progression-free and overall survival compared with the same drugs given every 3 weeks. Additionally, treatment with the angiogenesis inhibitor bevacizumab has shown significant antitumor activity in phase II studies. 

In this trial, patients with stage II, stage III, or stage IV ovarian epithelial, fallopian tube, or primary peritoneal cancer will be randomly assigned to receive one of three chemotherapy regimens: 

  • IV paclitaxel weekly and IV carboplatin every 3 weeks
  • IV paclitaxel weekly and IP carboplatin
  • IV paclitaxel and IP cisplatin, followed by IP paclitaxel

All patients will receive IV bevacizumab during and following chemotherapy. Doctors want to know which of these three regimens is most effective in delaying progression and improving survival.

“This trial is designed to determine if IP therapy is still superior given the clinical advances seen with regimens using weekly IV paclitaxel and/or bevacizumab,” said Dr. Walker. “The added benefit of weekly IV paclitaxel and bevacizumab, in combination, for women with ovarian cancer has the potential to be a very exciting advance.” 

For More Information
See the lists of entry criteria and trial contact information or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

An archive of "Featured Clinical Trial" columns is available at /clinicaltrials/ft-all-featured-trials.

Community Update

Operation Cessation: Curbing Military and Veteran Tobacco Use

A poster from the Department of Defense 'Quit Tobacco, Make Everyone Proud' campaign

The U.S. military has a long history with tobacco products. Cigarettes were issued in daily rations throughout World Wars I and II, and even into the Vietnam War. This unhealthy tradition came to a formal end in 1975, and today many military leaders hope that tobacco use will soon be just that—a thing of the past. The Department of Defense (DoD) has launched an online interactive tobacco cessation program that developers hope will help bring military tobacco use rates down.

Quit Tobacco, Make Everyone Proud promotes quitting tobacco as a matter of duty and pride and features campaign materials that convey two themes: role modeling and readiness. The campaign’s Web site and materials present service members as role models for their children and other loved ones, and senior leaders send strong messages about military readiness.

Rates of smoking in the military are higher than in the civilian population. According to a June 2009 Institute of Medicine (IoM) report commissioned by the Department of Veterans Affairs (VA) and the DoD, 32 percent of active duty military and 22 percent of all veterans smoke, compared with about 20 percent of the civilian adult population. Smoking rates are even higher among military personnel who have been deployed, and an increasing number of service members use smokeless tobacco products. 

The VA provides care for 6.7 million of the nation’s 24 million veterans and is the largest provider of care for adults with chronic psychiatric disorders, such as post-traumatic stress disorder. This population smokes at a very high rate, and the VA continues to invest in research on the most effective ways to provide tobacco cessation for these veterans. Researchers are also exploring policy interventions to promote tobacco cessation, such as further restricting the sale of tobacco products on military bases and increasing their price.

The June 2009 IoM report, titled “Combating Tobacco Use in Military and Veteran Populations,” includes numerous recommendations for the DoD and VA to make progress towards a tobacco-free military, and concludes that, “given the effects of tobacco use on military readiness and on the health of military personnel, retirees, their families, and veterans, the time has come for DoD and VA to assign high priority to tobacco control.” 

Quitting Tobacco and Reducing Stress

Active military personnel most often report using tobacco to relieve stress and boredom, said Dr. Keith Haddock, a veteran of the Air Force and senior principal investigator at the National Development and Research Institutes, Inc., who has studied the relationship between nicotine addiction and perceived feelings of stress, particularly among members of the military.

Using DoD survey data, Dr. Haddock and his colleagues looked at current smokers, former smokers, never smokers, and dual users (those who both smoked and used smokeless tobacco). They found that the more tobacco respondents used, the more stressful they considered their lives to be, both within and outside of military duty. Dual users reported the highest stress levels (Stein et al., Military Medicine 173(3), 2008).

“People who had quit smoking saw their lives, their work, and their deployment as less stressful than current smokers,” Dr. Haddock explained. Finally, tobacco users were more likely to use other negative coping behaviors (e.g., alcohol) and less likely to use positive coping strategies (e.g., problem solving) that those who did not use tobacco. The results, Dr. Haddock said, reinforce the evidence that tobacco use is not an effective method for coping with the stresses of military life and may actually make it less likely that soldiers will use positive coping strategies.

A Tailored Approach

The IoM report has raised awareness of additional opportunities for the VA and DoD to collaborate, emphasized Dr. Kim Hamlett-Berry, director of the VA’s Office of Public Health Policy and Prevention. “Our goal is to increase access to a menu of evidence-based options, so that any veteran who wants tobacco cessation resources can get them,” she said. “Our next steps are to take this even further and look at how the two systems could work together.”

This would build upon years of collaboration, particularly in the development of the DoD/VA Clinical Practice Guidelines, which draw upon evidence-based tobacco cessation tools and the specific prevention and treatment needs of both populations.

This commitment to tobacco cessation is reflected in the resources both departments provide to address tobacco addiction. All VA medical centers have tobacco cessation specialty clinics and use electronic medical records to build in clinical reminders for tobacco-use screening. The clinics provide free counseling and FDA-approved smoking cessation medications, including over-the-counter smoking cessation medications available on the Veterans Health Administration national formulary.

Veterans seen in primary care and outpatient mental health clinics are screened for tobacco use at least once a year. Providers offer brief cessation counseling to current tobacco users, as well as prescriptions for FDA-approved medications and referrals to more intensive counseling to assist veterans with quitting. 

The DoD’s Quit Tobacco, Make Everyone Proud campaign provides an opportunity to submit questions to tobacco cessation counselors in real time; computer games to distract from tobacco cravings; and short videos and audio podcasts—quitcasts and spitcasts—in which service members share testimonials and advice.

The U.S. Air Force’s (USAF) Wilford Hall Medical Center in San Antonio, TX, has developed a military-specific tobacco quitline currently being tested in an NIH-sponsored clinical trial. Col. Wayne Talcott, chair of the Department of Behavioral Medicine at the medical center, oversees the study, which provides quitline access to 27 USAF bases, including Osan Air Base in South Korea.

“My great hope is that this provides some flexibility so, when people are ready, they actually get help right away,” he said. “The bottom line is anybody who calls the quitline and who is a beneficiary of our healthcare system is going to get care—they don’t have to be at a particular location.”

Initial feedback indicates participants also appreciate reaching counselors who have first-hand military experience. “Having that feeling that you’re talking to someone who understands is an important part of this,” Col. Talcott said.

Dr. Robert Klesges of the University of Tennessee Health Science Center and the principal investigator of this study agreed that quitlines are an effective way to deliver smoking cessation services, and an effective way to reduce logistic barriers to accessing services. “A tobacco quitline or a tailored Internet program, military personnel can use anytime day or night. So a lot of what we are doing is tailoring these cessation tools to the intense job demands associated with the military,” Dr. Klesges commented.

Marching Forward on Tobacco Control

The challenge of reducing military tobacco use is especially large today, when many military personnel are or have been deployed in support of the war efforts in Afghanistan (Operation Enduring Freedom) and Iraq (Operation Iraqi Freedom). The tobacco control and prevention landscape within military and veteran communities is complex.

Tobacco use is prohibited in basic military training (BMT) in all branches of the military, and technical training programs following BMT often impose restrictions on tobacco use. But this prohibition often does not extend far beyond training, which can create a window for relapse or tobacco initiation. As many as 40 percent of junior enlisted smokers start using tobacco after joining the military, making prevention strategies a necessity and a challenge.

Dr. Klesges noted, “We had these nice cessation rates among our smokers—23 percent of those who smoked had quit, and 37 percent of those who used smokeless tobacco had quit—but the initiation among never smokers was so great, that we actually saw an increase in the prevalence of tobacco use.”

As the DoD and VA consider how to implement the IoM’s recommendations, researchers are trying to determine which types of tobacco interventions have the necessary support in this population. For example, the report encourages the military to treat tobacco use as it does other health-related behaviors that impair readiness, such as alcohol abuse and weight management. Dr. Klesges, who served on the committee that authored the report, put it plainly, saying, “We enforce weight standards, why wouldn’t we enforce tobacco-free standards?”

—Holly Aprea Gibbons

FDA Update

Another Use for the Cancer Drug Lapatinib

The FDA has approved the use of the drug lapatinib (Tykerb) in combination with letrozole (Femara) to treat postmenopausal women with advanced HER2-positive and hormone receptor (HR)-positive breast cancer. While these women in the past would have received some form of hormone-deprivation therapy alone, new evidence suggests that they may benefit from the addition of lapatinib. 

The evidence comes from a phase III clinical trial, EGF30008, comparing lapatinib plus the aromatase inhibitor letrozole with letrozole alone in women with advanced, metastatic breast cancer for whom hormone deprivation therapy was indicated. Women who received the combination treatment lived more than twice as long without their cancer progressing compared with those receiving letrozole alone (35 weeks versus 13 weeks).

Patients in the combination treatment arm also had superior rates of overall disease response and stable disease, the trial’s lead investigator, Dr. Stephen Johnston of the Institute of Cancer Research in the United Kingdom, told the NCI Cancer Bulletin in 2008. “These patients would previously be treated with endocrine therapy alone,” Dr. Johnston added. “Now the suggestion is that combined therapy may be a better approach.”

It is too early to know whether an improvement in overall survival will be observed in the clinical trial, the FDA noted in a statement.

“This drug combination of Tykerb plus Femara provides women being treated for advanced breast cancer with an important treatment option,” said Dr. Richard Pazdur, director of the FDA’s Office of Oncology Drug Products, in the statement. “This entirely oral treatment regimen works by targeting both HER2 and the hormone receptors, thereby slowing the cancer cells’ ability to grow or spread.”

NIH Update

NIH Clinical Center to Track Radiation Doses from Diagnostic Imaging

On February 1, the NIH Clinical Center announced in the Journal of the American College of Radiology that the amount of radiation patients receive during CT scans and other radiology procedures performed at the center will be recorded in their electronic medical records.

Scientists have recently expressed concerns that people may receive too much radiation from diagnostic imaging, and that such radiation exposure has been inadequately monitored.

“All vendors who sell imaging equipment to…the NIH Clinical Center will be required to provide a routine means for radiation dose exposure to be recorded in the electronic medical record. This requirement will allow cataloging of radiation exposures from these medical tests,” stated Dr. David A. Bluemke, director of the Clinical Center’s Radiology and Imaging Sciences, in an accompanying press release.

Vendors also must provide a means for radiation dose exposure to be tracked by patients in their own personal health records.

Too few patients are seen at the NIH Clinical Center for these data to provide a population-based assessment of cancer risk from low-dose radiation. For such a study, “the accumulation of medical testing doses of hundreds of thousands of individuals in the United States over many years will ultimately be necessary,” said Dr. Bluemke. “We encourage all medical imaging facilities to include similar requirements for radiation-dose-reporting outputs from the manufacturers of radiation-producing medical equipment.” Update

Online Course for Health Professionals on Clinical Trials

A new interactive, online course for health professionals, Including Clinical Trials in Your Practice, is now available from NCI. This free tutorial emphasizes the importance of clinical trials, discusses challenges clinical trial investigators face, and offers solutions to those challenges. The narrated tutorial includes eight different modules, case studies, and interactive exercises that address:

  • Becoming an investigator
  • Initial site preparation
  • Choosing the trial(s)
  • Building and training the research team
  • Handling site logistics
  • Recruiting and enrolling participants
  • Working with referring clinicians
  • Ensuring data integrity

With this course, oncologists will understand the process and steps involved in including NCI-sponsored clinical trials in their practice. Oncology practices, for instance, may likely find some of the modules helpful for determining whether clinical trials are a good fit for their practice. Other modules offer a better understanding of how to recruit, enroll, and retain patients in a trial. This course can also serve as an orientation or a refresher for oncology staff on best practices for including clinical trials in their practice.


NCI's Dr. Robert Wiltrout Named FLC's Lab Director of the Year

Dr. Robert Wiltrout Dr. Robert Wiltrout

NCI’s Dr. Robert H. Wiltrout has won the 2010 Laboratory Director of the Year award from the Federal Laboratory Consortium for Technology Transfer (FLC). This award is presented annually to directors who have made outstanding contributions to supporting technology transfer activities in the laboratory. Because of the competitiveness and prestige of the award, the honor recognizes both the award recipient’s efforts and his or her facility's technology transfer program.

Dr. Wiltrout, director of NCI’s Center for Cancer Research (CCR), also heads the Experimental Therapeutics Section in CCR’s Laboratory of Experimental Immunology. His work there focuses on understanding complex immune interactions in vivo and developing preclinical uses of immunotherapy, alone and in combination with other molecularly targeted strategies, for translation to clinical trials in cancer patients.

Dr. Wiltrout will receive the award April 29 at the FLC national meeting in Albuquerque, NM.

Learn about NCI's Cancer Biobank at caHUB Public Information Meetings

caHUB public meetings logo

In response to the lack of standardized, high-quality biospecimens for cancer research, NCI plans to develop a national cancer human biobank (caHUB). The aim of caHUB is to modernize the field of biobanking and contribute to medical advances by making high-quality human specimens and data available, as well as analysis, scientific tools, and services to the cancer research and product development communities.

NCI invites you to attend one of two public meetings to learn more about the caHUB planning process and mission, and review the implementation, structure, timeline, and funding process. Meeting dates and locations are:

February 19 from 8:30 a.m.–12:00 noon, ET
Natcher Auditorium, NIH main campus

March 1 from 8:30 a.m.–12:00 noon, PT
University of California, Los Angeles campus

To learn more, register, and view the videocast, please visit the caHUB meeting Web site.

NCI Symposium Will Look at Translational Genomics

Center of Excellence in Integrative Cancer Biology and Genomics logo

On March 4–5, the NCI Center of Excellence in Integrative Cancer Biology and Genomics will host a symposium titled, “Translational Genomics: Looking Back and Moving Forward.” Participants will gather in Natcher Auditorium on the NIH main campus to discuss ways to advance and implement novel technologies, develop clinical and bioinformatic infrastructures, and discuss how best to translate these technologies into clinical practice to improve the health of patients with cancer. Topics will include:

  • Critical assessment of translational genomics
  • Implementation of novel technologies
  • Infrastructure development

Abstracts are due by February 12. The event is free, but seating is limited so register online early. For additional information, contact Julia Lam.

World Cancer Day Observed on February 4

To recognize World Cancer Day on February 4, the International Union Against Cancer (UICC) launched “Cancer can be prevented too,” a global campaign to raise public awareness of cancer and how a number of simple steps can significantly reduce the risk of developing cancer:

  • Stop tobacco use and avoid exposure to second-hand smoke
  • Limit alcohol consumption
  • Avoid excessive sun exposure
  • Maintain a healthy weight through eating healthily and exercising regularly
  • Protect against cancer-causing infections

The 2010 campaign report highlights cancers that can be caused by infectious agents (viruses, bacteria, and other pathogens) and the means for intervention and prevention. This report is available electronically and in print, in English, French, and Spanish.

Celebrated each year, World Cancer Day is led by UICC and its member organizations, including NCI, with the support of the World Health Organization and key partners.

Learn about NCI’s global cancer research efforts on the Office of International Affairs Web site.

NCI and AACC Partner to Bridge the Gap between Lab and Clinic

NCI, through its Clinical Proteomic Technologies for Cancer (CPTC) initiative, has entered into a memorandum of understanding with the American Association for Clinical Chemistry (AACC) to promote and educate the clinical chemistry community in the area of proteomic standards and technology advances.

This partnership with AACC—an organization that represents professionals engaged in all aspects of clinical chemistry, from performing laboratory tests and analyses to developing new tests and laboratory devices—will provide an effective means for CPTC to educate clinical audiences on the need for and use of standards in multiplex-based proteomic technologies.

NCI established CPTC to address bias and variability in protein-based measurements (analytical, regulatory, and data release policies). This is being achieved through the development of new protein biomarker workflows that are reproducible, quantitative, and reliable. Through education and standardization of laboratory technologies, this partnership has the potential to reduce the amount of time and expenses needed to translate protein biomarker discoveries into clinical use.