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Cancer, Clinical Trials, In the News, NIH, Patient Care, Research

National Cancer Institute looking for “Exceptional Responders”

OLYMPUS DIGITAL CAMERAHope is a powerful force in cancer treatment. For patients and their families, the hope is that, no matter how unlikely, the treatment plan will cure the patient and eradicate the disease. Sadly, this is sometimes a long shot. But sometimes, against all odds, the therapy is unusually successful. Now the National Cancer Institute is trying to learn why.

This week the institute launched a study into the phenomena of “Exceptional Responders” – that is, cancer patients who have a unique response to treatments (primarily chemotherapy) that have not been effective for most other patients. As they describe in a Q&A about the effort:

For this initiative, exceptional responders will be identified among patients enrolled in early-phase clinical trials in which fewer than 10 percent of the patients responded to the treatments being studied; patients who were treated with drugs not found to be generally effective for their disease; patients who were treated in later-phase clinical trials of single agents or combinations; and even patients who were treated with established therapies. In this pilot study, malignant tissue (and normal tissue, when possible) and clinical data will be obtained from a group of exceptional responders and analyzed in detail. The goal is to determine whether certain molecular features of the malignant tissue can predict responses to the same or similar drugs.

The researchers would like to obtain tumor samples, as well as normal tissue, from about 100 exceptional responders. They’ll compare DNA sequences and RNA transcript levels and other molecular measurements to try to understand why these patients were such outliers in their response to treatment. In at least one previous case, an exceptional responder with bladder cancer led researchers to discover a new molecular pathway involved in the development of the disease, and suggested new therapeutic approaches for other similar patients.

Do you know someone who might qualify for the study? More from the Q&A:

Patients who believe they may be exceptional responders should contact their physicians or clinical trialists to see if they can assist in submitting tissue for consideration. [...] Investigators who have tissue from a potential exceptional responder should send an email to NCIExceptionalResponders@mail.nih.gov. The email should include a short description of the case, without patient identifiers; information about whether tissue collected before the exceptional response is available; whether informed consent was given to use tissue for research; and the patient’s vital status.

Photo by pol sifter

Cardiovascular Medicine, Genetics, Research, Science, Stanford News, Stem Cells

Stem cell study explains how mutation common in Asians affects heart health

Stem cell study explains how mutation common in Asians affects heart health

10011881004_d5ab6d7cd9_zMany Asians carry a mutation that causes their faces to flush when they drink alcohol. The affected gene is called ALDH2, and it also plays a role in cardiovascular health. Carriers are more susceptible to coronary artery disease and tend to recover more poorly than non-carriers from the damage caused by a heart attack. Now Stanford cardiologist Joseph Wu, MD, PhD, and postdoctoral scholar Antje Ebert, PhD, have learned why.

The researchers used a type of stem cell called an induced pluripotent stem cell, or iPS cell, to conduct the study. The stem cells are made from easily obtained tissue like skin, and they can be coaxed in the laboratory to become other types of tissue, like heart muscle cells. It’s one of the first times iPS cells have been used to examine ethnic-specific differences among populations. The research was published yesterday in Science Translational Medicine.

From our release:

The study showed that the ALDH2 mutation affects heart health by controlling the survival decisions cells make during times of stress. It is the first time ALDH2, which is involved in many common metabolic processes in cells of all types, has been shown to play a role in cell survival. In particular, ALDH2 activity, or the lack of it, influences whether a cell enters a state of programmed cell death called apoptosis in response to stressful growing conditions. [...]

The use of heart muscle cells derived from iPS cells has opened important doors for scientists because tissue samples can be easily obtained and maintained in the laboratory for study. Until recently, researchers had to confine their studies to genetically engineered mice or to human heart cells obtained through a heart biopsy, an invasive procedure that yields cells which are difficult to keep alive long term in the laboratory.

You’ve likely read about Wu’s previous work with heart muscle cells derived from iPS cells. Now he’s shown iPS cells are also a good way to compare the effect of genetic differences among populations, and he has big plans. More details about his plans from our release:

Wu is working to start a biobank at the Stanford Cardiovascular Institute of iPS cells from about 1,000 people of many different ethnic backgrounds and health histories. “This is one of my main priorities,” he said. “For example, in California, we boast one of the most diverse populations on Earth. We’d like to include male and female patients of major representative ethnicities, age ranges and cardiovascular histories. This will allow us to conduct ‘clinical trials in a dish’ on these cells, a very powerful new approach, to learn which therapies work best for each group. This would help physicians to understand for the first time disease process at a population level through observing these cells as surrogates.”

Previously: Induced pluripotent stem cell mysteries explored by Stanford researchers, A new era for stem cells in cardiac medicine? A simple, effective way to generate patient-specific heart muscle cells and “Clinical trial in a dish” may make common medicines safer, say Stanford scientists

Photo by Nicholas Raymond

Autoimmune Disease, Genetics, NIH, Research, Science

Tiny hitchhikers, big health impact: Studying the microbiome to learn about disease

Tiny hitchhikers, big health impact: Studying the microbiome to learn about disease

I don’t know about you, but I’m fascinated with the idea of the “microbiome.” If you’re unfamiliar with the term, it describes the millions upon millions of tiny, non-human hitchhikers that live on and in you (think bacteria, viruses, fungi and other microscopic life). Although the exact composition of these molecular roommates can vary from person to person, they aren’t freeloaders. Many are vitally important to your metabolism and health.

We’ve reported here on the Human Microbiome Project, launched in 2007 and supported by the National Institutes of Health’s Common Fund. Phase 2 of the project started last fall, with grants to three groups around the country to study how the composition of a person’s microbiome might affect the onset of diseases such as type 2 diabetes and inflammatory bowel disease, as well as its role in pregnancy and preterm birth. Now the researchers, which include Stanford geneticist Michael Snyder, PhD, have published an article in Cell Host & Microbe detailing what data will be gathered and how it will be shared.

As explained in a release by the National Human Genome Research Institute:

“We’re producing an incredibly rich array of data for the community from the microbiomes and hosts in these cohorts, so that scientists can evaluate for themselves with these freely available data which properties are the most relevant for understanding the role of the microbiome in the human host,” said Lita M. Proctor, Ph.D., program director of the Human Microbiome Project at NIH’s National Human Genome Research Institute (NHGRI).

“The members of the Consortium can take advantage of each other’s expertise in dealing with some very complex science in these projects,” she said. “We’re generating these data as a community resource and we want to describe this resource in enough detail so people can anticipate the data that will be produced, where they can find it and the analyses that will come out of the Consortium’s efforts.”

As I’ve recently blogged, data-sharing among researchers and groups is particularly important for research efficiency and reproducibility. And I’m excited to hear what the project will discover. More from the release:

For years the number of microbial cells on or in each human was thought to outnumber human cells by 10 to 1. This now seems a huge understatement. Dr. Proctor noted that the 10-to-1 estimate was based only on bacterial cells, but the microbiome also includes viruses, protozoa, fungi and other forms of microscopic life. “So if you really look at the entire microbial community, you’re probably looking at more like a 100-to-1 ratio,” she said.

Although thousands of bacterial species may make their homes with human beings, each individual person is host to only about 1,000 species at a time, according to the findings of the Human Microbiome Project’s first phase in 2012.

In addition, judging from the array of common functions of bacterial genes, if the bacteria are healthy, each individual’s particular suite of species appear to come together to perform roughly the same biological functions as another healthy individual. In fact, researchers found that certain bacterial metabolic pathways were always present in healthy people, and that many of those pathways were often lost or altered in people who were ill.

Stanford’s Snyder will join forces with researchers in the laboratory of George Weinstock, PhD, of the Jackson Laboratory for Genomic Medicine in Connecticut to investigate the effect of the microbiome on  the onset of Type 2 diabetes. Snyder may be uniquely positioned to investigate the causes of the condition. In 2012, he made headlines when he performed the first ever ‘omics’ profile of himself (an analysis that involves whole genome DNA sequencing with repeated measurements of the levels of RNA, proteins and metabolites in a person’s blood over time). During the process, he learned that he was on the cusp of developing type 2 diabetes. He was able to halt the progression of the disease with changes in exercise and diet.

Previously: Stanford team awarded NIH Human Microbiome Project grantElite rugby players may have more diverse gut microbiota, study shows and Could gut bacteria play a role in mental health?

Clinical Trials, Patient Care, Research, Science, Stanford News

Re-analyses of clinical trial results rare, but necessary, say Stanford researchers

Re-analyses of clinical trial results rare, but necessary, say Stanford researchers

The results of large clinical trials are used to make important clinical decisions. But the raw data on which these results are based are rarely made available to other researchers, perhaps due to concerns about intellectual property or giving a leg up to competitors in the field. But a new study by Stanford’s John Ioannidis, MD, DSci, shows that the re-analysis of such data by independent research is critical: About one third of the time it leads to conclusions that differ from those of the original study.

The research was published today in the Journal of the American Medical Association.

Clearly, data sharing is an important step in making sure research is conducted efficiently and renders reproducible results

For the study, Ioannidis and his co-authors surveyed about three decades of research cataloged in the National Library of Medicine’s PubMed database looking for re-analyses of previously published clinical-trial data. They found fewer than 40 studies that met their criteria (reanalyses using the original data to investigate a new hypothesis, or meta-analyses of several studies were not included) and, as I wrote in a release:

Thirteen of the re-analyses (35 percent of the total) came to conclusions that differed from those of the original trial with regard to who could benefit from the tested medication or intervention: Three concluded that the patient population to treat should be different than the one recommended by the original study; one concluded that fewer patients should be treated; and the remaining nine indicated that more patients should be treated.

The differences between the original trial studies and the re-analyses often occurred because the researchers conducting the re-analyses used different statistical or analytical methods, ways of defining outcomes or ways of handling missing data. Some re-analyses also identified errors in the original trial publication, such as the inclusion of patients who should have been excluded from the study.

Clearly, data sharing is an important step in making sure research is conducted efficiently and renders reproducible results – goals shared by the recently launched Meta-Research Innovation Center at Stanford (or METRICS), which Ioannidis co-directs. More from our release:

The fact that researchers conducting re-analyses often came to different conclusions doesn’t indicate the original studies were necessarily biased or deliberately falsified, Ioannidis added. Instead, it emphasizes the importance of making the original data freely available to other researchers to encourage dialogue and consensus, and to discourage a culture of scientific research that rewards scientists only for novel or unexpected results.

“I am very much in favor of data sharing, and believe there should be incentives for independent researchers to conduct these kinds of re-analyses,” said Ioannidis. “They can be extremely insightful.”

Previously: John Ioannidis discusses the popularity of his paper examining the reliability of scientific research, New Stanford center aims to promote research excellence and “U.S. effect” leads to publication of biased research, says Stanford’s John Ioannidis

Cancer, Dermatology, Research, Science, Stanford News

Skin cancer linked to UV-caused mutation in new oncogene, say Stanford researchers

Skin cancer linked to UV-caused mutation in new oncogene, say Stanford researchers

sunbathingA link between the UV rays in sunshine and the development of skin cancer is nothing new. We’ve all (hopefully) known about the damage sun exposure can wreak on the DNA of unprotected cells. But it’s not been known exactly how it causes cancers like squamous cell carcinoma or melanoma. Now, Stanford dermatologists Paul Khavari, MD, PhD and Carolyn Lee, MD, PhD have identified a UV-induced mutation in a protein active during cell division as the likely driver in tens of thousands of cases of skin cancer. Although the protein hasn’t been previously associated with cancer, the work of Khavari and Lee suggests it may actually be the most-commonly mutated oncogene in humans.

Their work was published yesterday in Nature Genetics. As we describe in our release:

Lee and Khavari made the discovery while investigating the genetic causes of cutaneous squamous cell carcinoma. They compared the DNA sequences of genes from the tumor cells with those of normal skin and looked for mutations that occurred only in the tumors. They found 336 candidate genes for further study, including some familiar culprits. The top two most commonly mutated genes were CDKN2A and TP53, which were already known to be associated with squamous cell carcinoma.

The third most commonly mutated gene, KNSTRN, was a surprise. It encodes a protein that helps to form the kinetochore — a structure that serves as a kind of handle used to pull pairs of newly replicated chromosomes to either end of the cell during cell division. Sequestering the DNA at either end of the cell allows the cell to split along the middle to form two daughter cells, each with the proper complement of chromosomes.

If the chromosomes don’t separate correctly, the daughter cells will have abnormal amounts of DNA. These cells with extra or missing chromosomes are known as aneuploid, and they are often severely dysfunctional. They tend to misread cellular cues and to behave erratically. Aneuploidy is a critical early step toward the development of many types of cancer.

The mutation in KNSTRN is a type known to be specifically associated with exposure to UV light. Khavari and Lee found the mutation in pre-cancerous skin samples from patients, but not in any samples of normal skin. This suggests the mutation occurs early, and may be the driving force, in the development of skin cancers. As Khavari, chair of the Department of Dermatology and dermatology service chief at the Veterans Affairs Palo Alto Health Care System, explained in the release:

Mutations at this UV hotspot are not found in any of the other cancers we investigated. They occur only in skin cancers… Essentially, one ultraviolet-mediated mutation in this region promotes aneuploidy and subsequent tumorigenesis. It is critical to protect the skin from the sun.

Previously: Master regulator for skin development identified by Stanford researchers and My pet tumor – Stanford researchers grow 3D tumor in lab from normal cells
Photo by Michael Coghlin

Big data, Evolution, Genetics, In the News, Research, Science, Stanford News

Flies, worms and humans – and the modENCODE Project

Flies, worms and humans - and the modENCODE Project

It’s a big day in comparative biology. Researchers around the country, including Stanford geneticist Michael Snyder, PhD, are publishing the results of a massive collaboration meant to suss out the genomic similarities (and differences) among model organisms like the fruit fly and the laboratory roundworm. A package of four papers, which describe how these organisms control how, when and where they express certain genes to generate the cell types necessary for complex life, appears today in Nature.

From our release:

The research is an extension of the ENCODE, or Encyclopedia of DNA Elements, project that was initiated in 2003. As part of the large collaborative project, which was sponsored by the National Human Genome Research Institute, researchers published more than 4 million regulatory elements found within the human genome in 2012. Known as binding sites, these regions of DNA serve as landing pads for proteins and other molecules known as regulatory factors that control when and how genes are used to make proteins.

The new effort, known as modENCODE, brings a similar analysis to key model organisms like the fly and the worm. Snyder is the senior author of two of the papers published today describing some aspects of the modENCODE project, which has led to the publication, or upcoming publication, of more than 20 papers in a variety of journals. The Nature papers, and the modENCODE project, are summarized in a News and Views article in the journal (subscription required to access all papers).

As Snyder said in our release, “We’re trying to understand the basic principles that govern how genes are turned on and off. The worm and the fly have been the premier model organisms in biology for decades, and have provided the foundation for much of what we’ve learned about human biology. If we can learn how the rules of gene expression evolved over time, we can apply that knowledge to better understand human biology and disease.”

The researchers found that, although the broad strokes of gene regulation are shared among species, there are also significant differences. These differences may help explain why humans walk, flies fly and worms slither, for example:

The wealth of data from the modENCODE project will fuel research projects for decades to come, according to Snyder.

“We now have one of the most complete pictures ever generated of the regulatory regions and factors in several genomes,” said Snyder. “This knowledge will be invaluable to researchers in the field.”

Previously: Scientists announce the completion of the ENCODE project, a massive genome encyclopedia

Cancer, Genetics, Research, Science, Stanford News

Unraveling the secrets of a common cancer-causing gene

Unraveling the secrets of a common cancer-causing gene

The Myc protein can cause a lot of trouble when it’s mutated or expressed incorrectly. Under those condition it’s called an oncogene, and it’s associated with the development of more than half of all human cancers. But because its cellular influence is vast (it controls the expression of thousands of genes and regulatory molecules), it’s been tough for scientists to learn which of its many effects are cancer-causing.

Now oncologist Dean Felsher, MD, PhD, and his colleagues have found that just a handful of genes are responsible for the Myc oncogene’s devastating outcomes. Their work was published today in Cancer Cell. As I wrote in our release:

The genes identified by the researchers produce proteins that govern whether a cell self-renews by dividing, enters a resting state called senescence or takes itself permanently out of commission through programmed cell suicide. Exquisite control of these processes is necessary to control or eliminate potentially dangerous tumor cells.

In particular, the researchers found that Myc works through a family of regulatory RNA molecules that govern how (and when) tightly packaged genes in the DNA/protein complex called chromatin are made available for transcription into proteins that do much of the work of the cell. Understanding this process might help researchers find ways to throw a molecular wrench into the Myc mechanism.

“One of the biggest unanswered questions in oncology is how oncogenes cause cancer, and whether you can replace an oncogene with another gene product,” Felsher told me. “These experiments begin to reveal how Myc affects the self-renewal decisions of cells. They may also help us target those aspects of Myc overexpression that contribute to the cancer phenotype.”

The reliance of many cancer cells on oncogenes like Myc is called oncogene addiction. In many cases, blocking the expression of an oncogene, or tinkering with its activity, causes cancer cells to stop growing and tumors in animals to regress. Recently Felsher and his colleagues published an article in the Proceedings of the National Academy of Sciences describing how inactivating two oncogenes at once can work better to fight cancer in animal models by making it more difficult for the cancer cells to develop resistance to therapy.

Previously: Tool to identify the origin of certain types of cancer could be a “boon to doctors prescribing therapies” and  Smoking gun or hit-and-run? How oncogenes make good cells go bad

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Evolution, Genetics, Obesity, Research, Science, Stanford News

Tiny fruit flies as powerful diabetes model

Tiny fruit flies as powerful diabetes model

Seung Kim

Fruit flies in your kitchen are unquestionably annoying. But the next time you’re trying to bat one out of the air around your too-ripe apples and bananas (or maybe that’s just me?), spare a few seconds to realize how important the tiny insects have been to science. They’ve been a darling of developmental biology for decades, as researchers identified genes (subsequently shown to be shared in mammals and humans) critically important in the metamorphosis from egg to animal. Frankly, it’s hard to over-estimate their contribution to science.

Now they’re set to take up a starring role in diabetes research. Stanford developmental biologist and Howard Hughes Medical Institute investigator Seung Kim, MD, PhD, and research associate Sangbin Park, PhD, have devised a way to measure insulin levels in fruit flies at the picomolar level – the level at which insulin concentrations are measured in humans. They’ve done so by successfully tagging the fruit fly insulin-like-peptide 2, or Ilp2, with a chemical tag. Their research was published today in PLOS Genetics.

From our release:

The experimental model is likely to transform the field of diabetes research by bringing the staggering power of fruit fly genetics, honed over 100 years of research, to bear on the devastating condition that affects millions of Americans. Until now, scientists wishing to study the effect of specific mutations on insulin had to rely on the laborious, lengthy and expensive genetic engineering of laboratory mice or other mammals.

In contrast, tiny, short-lived fruit flies can be bred in dizzying combinations by the tens of thousands in just days or weeks in small flasks on a laboratory bench.

In 2002, Kim and developmental biologist Roel Nusse, PhD, surprised many researchers when they showed that fruit flies develop a diabetes-like condition when their insulin-producing cells are destroyed. Further research has been stymied, however, by the difficulty of accurately measuring circulating insulin levels in the tiny animals. When speaking to me about the research, Kim called the new technique a “breakthrough” in the field.

Unlike many previous attempts by many groups, Park found two places in Ilp2 where the tag can be placed without affecting its biological activity. This allowed Kim and Park to track Ilp2 through its life cycle, as it’s produced by neurons in the brain (this is different from humans, who make insulin in beta cells in the pancreas), secreted into the blood stream and binds to insulin receptors in cells throughout the body. Parsing the effect of each mutation on the way the body produces, secretes and responds (or not) to insulin is critical to further understand the disease and to devise new therapeutic approaches. More from our release:

Park and his colleagues then turned their attention to mutations associated with type-2 diabetes in genome-wide studies in humans. These studies don’t reveal how a specific mutation might work to affect development of a disease; they show only that people with the condition are more likely than those without it to have certain mutations in their genome. Hundreds of candidate-susceptibility genes have been identified in this way.

Continue Reading »

Research, Science, Stanford News, Stem Cells

Induced pluripotent stem cell mysteries explored by Stanford researchers

Induced pluripotent stem cell mysteries explored by Stanford researchers

Induced pluripotent stem cells, also called iPS cells, made from easily accessible skin or other adult cells, are ideal for disease modeling, drug discovery and, possibly, cell therapy. That’s because they can be generated in large numbers and grown indefinitely in the laboratory. They also reflect the genetic background of the person from whom they were generated. However, some fundamental questions still remain before they’re ready for the full glare of the clinical limelight. Does it matter what type of starting cells scientists use to create the pluripotent stem cells? And what’s the best control to use when studying the effect of a particular, patient-specific mutation?

Now Stanford cardiologist Joseph Wu, MD, PhD, and his colleagues have addressed and answered these questions. Their work was published yesterday in two back-to-back papers in the Journal of the American College of Cardiology. (Each paper is also accompanied by an editorial.) As Wu explained in an e-mail to me:

If your goal is to generate healthy iPS cell derivatives for regenerative therapy, it’s important to know whether the starting material makes a difference. For example, if I’m treating Alzheimer’s disease, is there a benefit to using iPS cell-derived brain cells made from brain cells? Likewise, if I’m treating a skin disorder, is there a benefit to using iPS cell-derived skin cells made from skin cells? As cardiologists, we are asked this quite often and each time, I had to say “I don’t know.” So we decided to do a study comparing the differentiation and functional ability of iPS cell-derived cardiomyocytes generated from two different sources: skin and heart. We also wanted to devise more efficient ways for researchers to quickly and easily create their own “designer” iPS cell lines to study particular mutations.

To answer the first question, the researchers created iPS cells from two types of starter cells: human fetal skin cells and cardiac progenitor cells. Not surprisingly, only the cardiac progenitor cells expressed genes known to be expressed in heart tissue. Wu and his colleagues then exposed the newly created pluripotent stem cells to growing conditions that favor the development of heart muscle cells called cardiomyocytes. They found that, although iPS cells derived from cardiac progenitor cells were more efficient at becoming cardiomyocytes, both types of starting material produced heart muscle cells that functioned similarly after a period of growth in the laboratory. As Wu explained:

These two populations of cells are essentially no different from one another over time. It appears that they lost the memory of their starting material (this memory is stored in the form of chemical tags on the cells’ DNA in a phenomena known as epigenetic marking). This suggests that I could take my own skin cells, make iPS cells and then create specialized brain, heart, liver or kidney cells for cell therapy. This is much easier than biopsying each tissue, and could be a good way to create universal iPS cell lines for research or cell therapy.

In the second paper, Wu and his colleagues devised a way to introduce specific mutations into iPS cells before transforming them into particular tissues. The approach relies on the use of what’s known as “dominant negative” mutations that exert their disruptive effect even when the unmutated gene is still present. This is important because it’s much easier and quicker than previous similar efforts, which required a complicated, time-consuming procedure to snip out and then replace individual genes. The technique also allows researchers to generate two cell lines that are identical except for the mutation under study. That way researchers can be confident that differences between the cell lines are due only to that mutation, which is particularly important when the lines are used to test the effect of therapeutic drugs. Again, from Wu:

Investigators can make their own designer iPS cell lines to study particular mutations with genetically identical controls to use in their experiments. We won’t have to make new iPS cells from each patient, which is laborious and time consuming. Instead we can create standardized lines to study many different mutations alone and in combination. This has the potential to revolutionize the field of disease modeling and drug discovery.

The two papers describe ongoing research in the Wu lab designed to optimize iPS cells for a variety of applications. The group, including graduate student Arun Sharma, recently published research using human iPS cell-derived cardiomyocytes to investigate the effect of various antiviral drugs againse coxsackievirus, a leading cause of an infection of the middle layer of the heart wall in children and the elderly. The research is the first time that iPS cell-derived heart muscle has been used to investigate the mechanisms behind an acquired viral disease.

Previously: A new era for stem cells in cardiac medicine? A simple, effective way to generate patient-specific heart muscle cells, “Clinical trail in a dish” may make common medicines safer, say Stanford scientists and Lab-made heart cells mimic common cardiac disease in Stanford study

Cancer, Research, Science, Stanford News, Stem Cells

Radiation therapy may attract circulating cancer cells, according to new Stanford study

Radiation therapy may attract circulating cancer cells, according to new Stanford study

Localized radiation therapy for breast cancer kills cancer cells at the tumor site. But, in a cruel irony, Stanford radiation oncologist Edward Graves, PhD, and research associate Marta Vilalta, PhD, have found that the dying cells in the breast may send out a signal that recruits other cancer cells back to the site of the initial tumor. Their work was published today in Cell Reports. As Graves explained in an e-mail to me:

Cancer spreads by shedding tumor cells into the circulation, where they can travel to distant organs and form secondary lesions.  We’ve demonstrated with this study that cancer radiation therapy may actually attract these circulating tumor cells, or CTCs, back to the primary tumor, which may lead to the regrowth of the tumor after radiation therapy.

The researchers studied mouse and human breast cancer cells growing in a laboratory dish, as well as human breast cancer cells implanted into mice. They found that irradiated cells secreted a molecule called granulocyte macrophage colony stimulating factor, or GM-CSF. Blocking the expression of GM-CSF by the cells inhibited (but didn’t completely block) their ability to recruit other cells to the cancer site. The finding is particularly interesting, since physicians sometimes give cancer patients injections of GM-CSF to enhance the growth of infection-fighting white blood cells that can be damaged during chemotherapy. As Graves explained, “This work has important implications for clinical radiotherapy, and for the use of GM-CSF in treating neutropenia in cancer patients during therapy.”

The researchers say, however, that cancer patients shouldn’t eschew radiation therapy. Rather, the finding may help clinicians devise better ways to fight the disease – perhaps by blocking GM-CSF signaling. Graves concluded:

It should be emphasized that radiation therapy remains one of the most effective treatments for cancer. Our findings will help us to further optimize patient outcomes following this already potent therapy.

Previously: Using 3-D technology to screen for breast cancer, Blood will tell: In Stanford study, tiny bits of circulating tumor DNA betray hidden cancers and Common drug class targets breast cancer stem cells, may benefit more patients, says study

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