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Cancer, Clinical Trials, Pediatrics, Public Health, Research

Researchers call for broader age limits for cancer trials to increase participation of teenage patients

Researchers call for broader age limits for cancer trials to increase participation of teenage patients

Findings published today in the Lancet Oncology highlight the need to increase the flexibility of age limits for cancer trials so that more teenage patients have access to experimental treatments. “Right now too many of our young patients are needlessly falling through the gap between paediatric and adult cancer trials,” said Lorna Fern, PhD, who led the study and co-ordinates research for the Teenage and Young Adult Clinical Studies Group of the UK-based National Cancer Research Institute.

In the study (subscription required), researchers examined strategies to boost participation of teens and young adults diagnosed with cancer in clinical trials. The study involved 68,275 patients, aged 0-59 years, who were diagnosed with cancer within a five-year window. According to a release:

The study showed [trials designed with broader age limits] led to a 13 per cent rise in 15-19 year old cancer patients taking part in clinical trials between 2005 and 2010 (from 24 to 37 per cent), and a five per cent rise in 20-24 year olds (from 13 to 18 per cent). Children under 14 taking part in trials rose by six per cent (from 52 to 58 per cent).

This rise was due to the increase in availability and access to trials for young people, increased awareness from healthcare professionals, patients and the public about research and importantly the opening of trials with broader age limits which allow older teenagers and young adults to enter trials.

Fern added, “By encouraging doctors to take into account the full age range of patients affected by individual types of cancer, we’ve shown that it’s possible to design trials that include teenage cancer patients and, importantly, that better match the underlying biology of the disease and the people affected.”

Previously: High rates of incarceration among black men could be skewing study results, Stanford researchers examine disparities in use of quality cancer centers and NPR explores the need for improving diversity in clinical trials

Cancer, Research, Stanford News

Tool to identify the origin of certain types of cancer could be a “boon to doctors prescribing therapies”

Tool to identify the origin of certain types of cancer could be a "boon to doctors prescribing therapies"

A team of Stanford scientists has developed a tool to identify the biological signatures in cancer cells that can be traced back to the original cancer gene. As noted today in a Stanford Report story, the tool could help unravel the secrets of cancer and be “a boon to doctors prescribing therapies for their patients.”

For the study, researchers examined an oncogene that is related to lymphoma and responsible for roughly 50 percent of all human cancers. An oncogene is a gene that can cause a normal cell to become cancerous when mutated, or be expressed at abnormally high levels. The team hoped to find a biological signature that would trace the mutating cancer cells back to the original oncogene. More from the article about the work:

Using an elegant statistical method from Robert Tibshirani, [PhD,] professor of health research and policy (biostatitstics) and of biostatistics, the team was able to identify not just one but 86 lipids that can be traced back to the oncogene.

“It’s not just diagnostic,” [postdoctoral researcher Livia Eberlin, PhD,] said. “It gives extra information that could be prognostic.”

Depending on the bio-signature of the cancer cells, physicians will have a better idea of the aggressiveness of a patient’s cancer. In the future, this research may lead to a better knowledge of cancer in general.

“The next step,” said [Dean Felsher, MD, PhD,] professor of medicine (oncology) and of pathology, one of the team members from Stanford School of Medicine, “is to use this as a way to figure out the causal mechanism.” Though the connection between the cancer cells and their origin is clear, the actual cause of cancer – the biological trigger that pushes cancer to progress – is still mysterious.

The study is scheduled to be published in Proceedings of the National Academy of Sciences.

Previously: Smoking gun or hit-and-run? How oncogenes make good cells go bad, Cellular culprit identified for invasive bladder cancer, according to Stanford study and Blood will tell: In Stanford study, tiny bits of circulating tumor DNA betray hidden cancers

Cancer, FDA, Genetics, Research, Science, Stanford News

Another blow to the Hedgehog pathway? New hope for patients with drug-resistant cancers

Another blow to the Hedgehog pathway? New hope for patients with drug-resistant cancers

6825694281_dfb79615d6_zIf you’re a regular reader of this blog, or follow cancer literature, you’ll have heard of a signaling pathway called Hedgehog that is activated in many cancers, including brain, skin and even bladder. It’s a cute name for cellular cascade that can kill when inappropriately activated.

Neurologist Yoon-Jae Cho, MD, treats children with brain tumors called medulloblastomas. He and postdoctoral fellow in his lab, Yujie Tang, PhD, published a study yesterday in Nature Medicine that could one day help some patients whose Hedgehog-driven tumors have become resistant to available therapies.

As Cho explained in an e-mail to me:

Medulloblastomas are the most common malignant brain tumors in children. They are comprised of various subgroups, including one with activation of a strong oncogenic signal called the Hedgehog pathway. Notably, the Hedgehog pathway is also activated in several other cancers including basal cell carcinoma, the most common cancer worldwide. Therefore, pharmaceutical companies and several research groups have developed drugs to target this pathway.

The most common of these drugs targets a downstream protein component of the pathway called Smoothened, including one currently marketed by Genentechcalled vismodegib (trade name Erivedge) and an investigational drug produced by Novartis called LDE225. Blocking the activity of Smoothened stops the chain reaction leading to division of the cancer cells. You can think of it (in simplified terms) as a line of dominoes standing on end, waiting for an eager finger to begin the chain reaction. Removing one domino (nixing Smoothened activity) can sometimes stop the rest of the row from falling and block the cancerous cell from dividing. But, as Cho explained:

Unfortunately, many cancers activate the Hedgehog pathway downstream of Smoothened and are inherently resistant to these therapies. Other cancers that are initially responsive to these drugs develop resistance through activation of downstream Hedgehog pathway components.

Cho and his colleagues have now described a new, novel way to interfere with the Hedgehog pathway. They’ve found that compounds that inhibit a protein called BRD4 can stop the growth of human Hedgehog-driven cancers – even when they’re resistant to drugs blocking Smoothened activity. This is particularly interesting because the BRD family of proteins recognizes and binds to particular chemical tags on chromatin that control whether (and when) a gene is made into a protein. It’s the first time such an epigenetic regulator has been implicated as a target in the Hedgehog pathway. Additionally, it’s a new avenue to explore for patients with Hedgehog-driven medulloblastomas – as many as half of whom will be resistant to Smoothened inhibition, according to a previous study co-authored by Cho and members of the International Cancer Genome Consortium’s Pediatric Brain Tumor Project. Cho concludes, “Our study offers a promising new treatment strategy for patients with Hedgehog-driven cancers that are resistant to the currently used Smoothened antagonists.”

Previously: New skin cancer target identified by Stanford researchers, Humble anti-fungal pill appears to have noble side-effect: treating skin cancer and Studies show new drug may treat and prevent basal cell carcinoma
Photo by Phillip Taylor

Big data, Cancer, Research, Science, Stanford News, Videos

Will hypothesis or data-driven research advance science? A Stanford biochemist weighs in

Will hypothesis or data-driven research advance science? A Stanford biochemist weighs in

The 2014 Big Data in Biomedicine conference was held here last month, and keynote speakers, panelists, moderators and attendees are now available on the Stanford Medicine YouTube channel. To continue the discussion of how big data can be harnessed to benefit human health, we’ll be featuring a selection of the videos this month on Scope.

Julia Salzman, PhD, a Stanford assistant professor of biochemistry, is concerned that significant amount of data is being thrown in the trash “because the data don’t fit our sense of what they should look like.” At Big Data in Biomedicine 2014, she explained how giving her computers a long leash led her down an unexpected path and the discovery of a new, and probably noteworthy, biological entity. My colleague Bruce Goldman highlighted her findings in a news release:

Using computational pattern-recognition software, her team discovered numerous instances in which pieces of RNA that normally are stitched together in a particular linear sequence were, instead, assembled in the “wrong” order (with what’s normally the final piece in the sequence preceding what’s normally the first piece, for example). The anomaly was resolved with the realization that what Salzman and her group were seeing were breakdown products of circular RNA — a novel conformation of the molecule.

In its circular form, she noted, an RNA molecule is much more impervious to degradation by ubiquitous RNA-snipping enzymes, so it is more likely than its linear RNA counterparts to persist in a person’s blood. Every cell in the body produces circular RNA, she said, but it seems to be produced at greater levels in many human cancer cells. While its detailed functions remain to be revealed, these features of circular RNA may position it as an excellent target for a blood test, she said.

In the above Behind the Scenes at Big Data video, Salzman discusses her work and addresses a question asked during the Single Cells to Exacycles panel: In this next era of science, will science advance mainly through hypothesis or data driven research? She comments, “I think that’s a fundamental question moving forward, whether the scientific method is dead or whether it’s still alive and kicking. I think that’s a really important question for us as to answer and deal with as scientists.” Watch the interview to find out the rest of Salzman’s thoughts on the issue.

Previously: Rising to the challenge of harnessing big data to benefit patients, Discussing access and transparency of big data in government and U.S. Chief Technology Officer kicks off Big Data in Biomedicine

Cancer, NIH, Public Health, Research, Stanford News, Videos

NIH associate director for data science on the importance of “data to the biomedicine enterprise”

NIH associate director for data science on the importance of "data to the biomedicine enterprise"

The 2014 Big Data in Biomedicine conference was held here last month, and interviews with keynote speakers, panelists, moderators and attendees are now available on the Stanford Medicine YouTube channel. To continue the discussion of how big data can be harnessed to benefit human health, we’ll be featuring a selection of the videos this month on Scope.

During his keynote speech at Big Data in Biomedicine 2014, Philip Bourne, PhD, the first permanent associate director for data science at the National Institutes of Health, shared how the federal agency hopes to capitalize on big data to accelerate biomedicine discovery, address scientific questions with potential societal benefit and promote open science.

In the above video, he talks about how data “is becoming increasingly important to the biomedical enterprise” and the NIH’s effort to coordinate strategies related to computation and informatics in biomedicine across its 27 institutes and centers, which effectively form the basis of improvements in health care across every major medical condition. “Our goal is to create interoperability between these entities,” he says in the interview. “We see data as the catalyst to create this cross talk across these respective institutes.”

Previously: Rising to the challenge of harnessing big data to benefit patients, Discussing access and transparency of big data in government and U.S. Chief Technology Officer kicks off Big Data in Biomedicine

Cancer, Health and Fitness, Stanford News

The ride of his life: Local cyclist races across the country to benefit Stanford Cancer Institute

John Tarlton big

Menlo Park businessman John Tarlton is on the ride of his life, attempting to bike 3,000 miles across the country in 12 days. He’s competing in the Race Across America (RAAM), one of the world’s most extreme endurance events. RAAM originated in 1982 as four cyclists raced from the Santa Monica Pier to the Empire State Building.

“I have dreamed of competing in RAAM since childhood,” Tarlton told me by e-mail prior to the race. As of this post, he is more than halfway through, having biked more than 1,800 miles in about six and a half days.

Tarlton, 45, a lifetime cycling enthusiast, has been preparing for RAAM for several years. The RAAM course is nearly 50 percent longer than the Tour de France, though completed in about half the time. And unlike the Tour de France riders, who rest and refuel at their hotels each night, most RAAM riders can’t afford to sleep more than four hours a day, since every minute counts against the 12-day time limit. Eating presents an interesting challenge: Tarlton, a lean vegetarian, estimates he’ll need to consume 16,000 calories per day (and no, that’s not a typo!) during the race.

Like many RAAM riders and teams, Tarlton is using interest generated by this event to raise awareness and dollars for a cause – in this case, cancer, which has affected both his and his supports team’s families. Donations made in honor of Tarlton’s effort will support the Stanford Cancer Institute.

Since I mostly ride an indoor stationary bike with a TV screen affixed, I had a few questions for this ultra-driven athlete. Below are Tarlton’s answers provided by e-mail and lightly edited:

Describe your typical training day.

There really is no “typical” training day for me. Some days I only ride the bike for one hour, spend another hour weight training and then two hours doing recovery activities. Other days I will be on the bike for 14 hours straight.

What is the biggest challenge during the race?

It is hard to predict. Some years, there have been lightening storms that require riders to hide inside cars, while other years there are strong headwinds for extended periods of time. Our biggest challenge will be to adapt to whatever nature throws at us, in addition to any unexpected equipment failures, while sticking to our plan.

Besides finishing, what’s your goal for the race?

We hope to raise quite a bit of money for Stanford Cancer Institute. In all honesty, the goal of completing the race within the allotted 12 days is such an overarching goal, that any other athletic goals would pale in comparison.

Why did you choose to benefit the Stanford Cancer Institute (SCI)?

SCI is at the forefront of the cancer treatment effort, from cutting-edge primary research to new ways of focusing on the patient during recovery. My professional life revolves around buildings for life science research and commercialization. The partnership between Tarlton Properties and SCI seems a natural fit.

My family has been deeply affected by cancer and has strong ties to Stanford. My parents met in the Stanford Choir in 1954, and my father is a past president of Stanford Associates. My wife, Jenny Dearborn, graduated from the Stanford Teacher Education program; her father attended Stanford and her grandfather was a professor there.

Finally, Stanford doctors were central to the care of my mother and sister, as well as my crew chief’s wife, during their battles with cancer.

Continue Reading »

Cancer, Pediatrics, Research

Study highlights childhood cancer survivors’ increased risk of future health problems

Study highlights childhood cancer survivors' increased risk of future health problems

New research shows that childhood cancer survivors are hospitalized more frequently, and for longer durations, decades after their initial cancer diagnosis as compared to those without a history of cancer. Based on the findings, study author Anne Kirchhoff, PhD, MPH, assistant professor of pediatrics at the University of Utah, advised that patients and families “who have experienced childhood cancer should obtain a cancer treatment summary and recommendations for follow-up care from their oncologist, and coordinate their follow-up care with their oncology and primary care doctors to ensure their health care needs are being managed.”

For the study, which was published in Cancer Epidemiology, Biomarkers & Prevention, Kirchhoff and colleagues recruited nearly 1,500 childhood cancer survivors who were at least five years past their original cancer diagnosis and more than 7,000 individuals who did not have cancer, who served as the control group. According to an American Association for Cancer Research release, study results showed:

… survivors were 52 percent more likely to be hospitalized, and their number of admissions was 67 percent higher, compared with age and sex-matched individuals who did not have cancer. Survivors were also 35 percent more likely to have stayed longer every time they were hospitalized, compared with controls.

More than 10 percent of survivors of central nervous system tumors, neuroblastoma, or malignant bone tumors were hospitalized five or more times during the follow-up period, and the hospital admission rates were approximately two times higher for survivors of neuroblastoma and bone tumors, respectively, compared with controls. “We saw higher rates of hospitalization across most cancer types, but not for all cancers, which gives us clues as to which groups of survivors may need better surveillance in the long term,” said Kirchhoff.

Common reasons for hospitalizations for survivors compared with the controls included conditions like blood disorders (such as anemia) and cancer, although it is unclear if this was for their original cancer diagnosis or new cancers. Infections, nervous system problems, and respiratory problems were other leading reasons for hospitalization.

To follow up on these findings, researchers are planning to further study the reasons survivors are hospitalized and the costs associated with these visits.

Previously: New Stanford-developed method finds tumors in children without exposing them to radiation, Questioning whether physicians are equipped to care for childhood cancer survivors, Cancer survivor: The disease isn’t a “one-off, one-shot deal”, and Surviving pediatric brain cancer

Cancer, In the News, Patient Care

“You have cancer”: On being a doctor and receiving the news

"You have cancer": On being a doctor and receiving the news

Inquiring patients might want to know what their doctors would do for themselves in certain medical situations. (And, as recently discussed here, the answers might be surprising.) An article in this morning’s San Francisco Chronicle surveys oncologists and other cancer specialists who have been diagnosed with a disease they study or treat. It describes how they respond to the news “You have cancer” – and if or how they choose to share their personal experiences with patients.

From the piece:

As a pathologist, [Kimberly Allison, MD, associate professor of pathology] typically sees patients’ cells, rather than the patients themselves.

So it’s not surprising that when she had a biopsy on her breast after noticing tissue changes in 2008, her first reaction was to be excited to see her own sample under the microscope. She assumed the sample would be benign, but when her colleagues came to her with the results, looking grim, she knew it was bad.

“I knew I needed to be worried,” said Allison, who is now at Stanford but was working at the University of Washington in Seattle at the time. “I knew I was going to get aggressive treatment, but I was terrified about what that might be like. That fear was just the same as in any patient.”

The article goes on to describe how Allison found support from fellow patients and even wrote a book about her experience with the disease. Her specialized knowledge of cells proved to be a key weapon against her illness:

She could look at her cancer cells under the microscope before they were wiped out by the treatments.

“Whenever I felt like I wanted to talk smack to it, I would look at it,” she said. “I’d tell it, ‘I never want to see you again.’ “

Previously: A doctor recounts his wife’s battle with cancer: “My knowledge was too clear-eyed”, A Stanford physician’s take on cancer prognoses – including his own, Both a doctor and a patient: Stanford physician talks about his hemophilia and Red Sunshine: One doctor’s journey surviving stage 3 breast cancer

Cancer, Research, Science, Stanford News

Smoking gun or hit-and-run? How oncogenes make good cells go bad

Smoking gun or hit-and-run? How oncogenes make good cells go bad

Smoking gun

It can be tough to find the mutations responsible for turning a normal cell cancerous. By the time a tumor has been diagnosed and analyzed, its cells have undergone many, many rounds of DNA replication and division – likely accumulating mutations all the while. But oncogenes (mutated versions of normal genes often associated with cell division) have been identified as the smoking gun in many cancers, some are viewed as attractive targets for cancer therapies because their effects on cell growth appear so pervasive.

Now new research is beginning to suggest a cancer cell’s reliance on oncogenes and other mutations may be much more nuanced than originally believed. Stanford oncologists Ash Alizadeh, MD, PhD, and Michael Green, PhD, study diffuse B-cell lymphoma, which is the most-common aggressive lymphoma in this country. About half of all people diagnosed with the condition will die from the disease. (Stanford’s Lymphoma and Hodgkin’s Disease Research Program treats many patients with this and other blood cancers.)

In 2000, Alizadeh showed that cancer cells from patients with diffuse B-cell lymphoma fall into two subsets when categorized by their gene expression profiles. One, the germinal center B-cell like (or GCB-like) subset has a much better prognosis than the other, which more closely resembles the gene profile seen in activated B-cells (ABC-like). But the basis of the prognostic differences between the two groups has not been known.

In the new study, which was published this week in Nature Communications (subscription required), Alizadeh and Green investigate the role of an oncogene called Bcl6 in diffuse B cell lymphoma. Their research suggests that, in at least one of the subcategories of this type of lymphoma, the reliance on the Bcl6 oncogene is limited to very early stages of development, before the cells themselves had completely matured.

As Green explained in an e-mail to me:

This work adds to growing evidence that the two subtypes of diffuse large B-cell lymphoma, which have very different clinical outcomes, may in fact be two genetically distinct diseases. There were also a number of surprises in this project. In particular, the notion that expression of an oncogene for a limited period in a stem cell is capable of reprogramming those cells towards becoming cancer at a later stage of development is a completely new paradigm. Now we have to ask ourselves whether we should be thinking differently about how lymphoma, and maybe cancer in general, evolves.

This type of hit-and-run hypothesis is different from the traditional view of how oncogenes work, Alizadeh explained in an e-mail:

 The results from this study clearly illustrate that, if cancers can result via ”hit-and-run” oncogenesis, oncogenes that initiate tumor formation might be dispensable for tumor cell survival and/or tumor progression. In this context, mutations that activate oncogenes would have a driving role in the tumorigenic process, but may act as passenger mutations thereafter, or may have a secondary role in evolved tumor cell clones. This may provide an explanation for the failure of some modern targeted therapies to clear tumor progenitor cells, despite being effective agents against evolved tumor cells. As a consequence, targeted treatment strategies may need to be altered to accommodate combinations of agents that target oncogenic pathways that are active at both the early and late stages of tumor development.

Their research was conducted in collaboration with researchers in the laboratory of Isidro Sanchez-Garcia, MD, PhD at the Institute of Biomedical Research of Salamanca in Spain.

Previously: Cellular culprit identified for invasive bladder cancer, according to Stanford study,  Blood will tell: In Stanford study, tiny bits of circulating tumor DNA betray hidden cancers, and Leukemia prognosis and cancer stem cells
Photo by brett jordan

Cancer, Dermatology, Events, Public Health, Stanford News

Free skin cancer screening being held Saturday

Free skin cancer screening being held Saturday

sunbatherScreening for skin cancer is advised for people with many moles or atypical moles, fair skin or a history of excessive sun exposure, a personal history of skin cancer or precancerous spots, or a parent or sibling who has had skin cancer. Each year, Stanford dermatologists offer a free screening for those in the local community, and this year’s event – being held tomorrow, May 31 – will offer more than the experienced eyes of skin clinicians.

Understanding that many people have concerns about one particular spot, the organizers are debuting a form of fast-track evaluation for just such concerns. During the Spot Check service, clinicians will use and study a new Stanford-developed smartphone-based device. As Justin Ko, MD, co-chief of medical dermatology at Stanford Hospital & Clinics, explained to me, “The device allows a user to capture clinical images of a skin lesion with their smartphone previously possible only with specialized, expensive devices typically used by dermatologists. We’ll be doing some studies to validate what we believe may well ‘democratize’ ability to capture and send medical-quality images of skin lesions by making this technology accessible and easy to use.”

The screening event (.pdf) will also include information on SUNSPORT, a collaboration of the Stanford Cancer Institute, the medical school’s Department of Dermatology, Stanford Athletics, and Stanford Hospital & Clinics, which provides student-athletes with information about their heightened risks for sun-related skin damage and works with the teams’ coaches and athletic trainers to reinforce skin-protection practices on a daily basis.

For local readers: The event runs from 8-11 AM at the Stanford Medicine Outpatient Center in Redwood City. Call (650) 723-6316 for more information.

Previously: Skin cancer images help people check skin more often and effectively, Working to protect athletes from sun dangersStanford clinic addresses cancer-related skin issuesAs summer heats up take steps to protect your skin and Man’s story shows how cancer screenings saves lives
Photo by Tom Godber

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