The study, which was undertaken by researchers at Kanazawa University and the Japan Agency for Medical Research and Development, expands upon research which began in 1982 that reported a link between chronic gastritis and stomach bacterium Helicobacter pylori, triggering a flurry of research into this newly-identified pathogen.

These studies made it clear that in addition to its involvement in gastritis, H. pylori was a significant factor in the development of both peptic ulcers and gastric cancer. But while the link between the bacterium and disease was clear-cut, exactly how H. pylori caused gastric tumours remained the subject of much debate.

Now, four decades later, the link has finally been explained. 

“We previously showed that tumour necrosis factor alpha (TNF-α), a cytokine that causes inflammation, promotes gastric tumour formation by activating a protein called NOXO1,” said lead author of the study Dr Kanae Echizen. “What we didn’t know was exactly how NOXO1 induces tumour formation in the stomach.”

NOXO1 is a component of the NOX1 complex, which produces tissue-damaging molecules called reactive oxygen species (ROS). This can result in mutations in the DNA of stomach cells, leading to tumour formation. Inflammation caused by H. pylori infection also produces ROS, increasing oxidative stress in the stomach.

The researchers showed that inflammation caused excess production of NOX1-complex proteins in response to signals from NF-κB, a regulatory protein that turns on genes to combat stress or bacterial infection, and which is a major player in the inflammatory response. They also found that NOX1/ROS signalling caused gastric epithelial stem cells to multiply uncontrollably, resulting in tumour formation.

Knowing this, the researchers used a drug to suppress the activity of the NOX1 complex, which halted the growth of gastric cancer cells. Even more excitingly, disruption of NOXO1 in a mouse gastritis model stopped the proliferation of epithelial stem cells.

“We have finally been able to show that inflammation enhances the expression of NOXO1, which induces the proliferation of gastric epithelial stem cells, leading to gastric tumours,” Dr Masanobu Oshima, senior author of the study explained. “Gastric cancer is the fourth most common cancer worldwide and has the second highest mortality rate. If we can disrupt the NOX1/ROS signaling pathway in situ, we may be able to prevent the development of this aggressive disease.”

For further details of the study click here. 


Despite significant advances, only a minority of individuals benefit from immunotherapy to treat cancer, and the reasons why remain unclear.

Immunotherapy research has largely centred on T cells, a type of immune cell that learns to recognise specific proteins and launch an attack. Tumours, however, are a complex mixture of many different cell types, including other immune cells known collectively as tumour-infiltrating myeloid cells. These cells represent alternative targets for immunotherapy, but their role in tumours is still poorly understood.

To shed light on this under-examined family of immune cells, Harvard Medical School researchers based at the Blavatnik Institute, Massachusetts General Hospital, Beth Israel Deaconess Medical Center and Brigham and Women’s Hospital used single-cell sequencing to map the landscape of myeloid cells in tumours from patients with lung cancer.

Their study, published in the journal Immunity, reveals 25 myeloid cell subpopulations, many previously undescribed, with distinct gene expression signatures that are consistent across patients. Most of these subpopulations were also identified in a mouse model of lung cancer, indicating a high degree of similarity in myeloid cells across species.

The findings serve as a foundation for future research to explain the precise roles of myeloid cells in cancer and to assess their potential as targets for new or improved immunotherapies, the authors said.

“Immunotherapy is clearly a transformational approach to cancer treatment, but there are many patients who don’t respond, and the question is why,” said co-corresponding author Allon Klein, assistant professor of systems biology at HMS.

“Part of the answer could certainly lie at the level of myeloid cells, which interact heavily with both tumour cells and T cells,” Klein continued. “By identifying the rich complexity of myeloid cell states in tumours, we now have a powerful starting point to better understand their functions and clinical applications.”

Of particular importance, the authors said, was the finding that myeloid subpopulations can be reliably identified in different human patients and in mice – an observation that underscores the fundamental use of mouse models in immunotherapy research.

“Tumour cells were different in each patient analysed, but the identity of tumour-infiltrating myeloid cells greatly overlapped between the same patients. Also, many myeloid populations were incredibly well conserved across patients and mice,” said co-corresponding author Mikael Pittet, HMS associate professor of radiology at Mass General.

“This is exciting because a growing body of evidence based on mouse studies suggests that myeloid cells can control cancer progression and affect virtually all types of cancer therapy, including immunotherapy” Pittet added.

Myeloid cells – comprised of immune cells including monocytes, macrophages, dendritic cells and granulocytes – are part of the innate immune system, the body’s first and broad line of defence against foreign pathogens. They play an important role in activating the adaptive immune system, including T cells, which can precisely target and destroy pathogens.

Their analyses revealed myeloid cell gene expression signatures that fell into 25 distinct clusters, greatly expanding the number of known myeloid cell states.

They found that dendritic cells, for example – which Pittet and colleagues previously found are critical to successful anti-PD-1 immunotherapy in mice – contained four different subtypes that are largely mirrored between humans and mice. Monocyte subtypes also matched well between humans and mice, while macrophages were both conserved and varied by species.

Neutrophils, which are the most abundant white blood cells in mammals, formed a spectrum of five similar subtypes in humans and mice, with one subset unique to mice. Pittet, in a previous collaboration with Klein, found that neutrophils expressing high levels of the gene Siglecf have tumour-promoting properties. The new analyses corroborated this finding, showing that these neutrophils are highly enriched in tumours.

“Myeloid cell populations are complex, but we see the same complexity across patients and species, which gives us confidence that insights in mouse models can be translated to humans,” said Pittet.

With the landscape of myeloid cell gene-expression patterns mapped, scientists can mine existing datasets of patients with known clinical outcomes to look for the presence of a given population of myeloid cells and assess their relationship with patient survival.

The team also looked at whether the behaviour of myeloid cells in tumours could be gleaned by sampling myeloid cells circulating in blood and found a poor relationship between the two.

In addition to immediate basic and translational research opportunities, the study findings inform the work of initiatives such as the Human Tumor Atlas, an effort to map the landscape of all cell types in the human body, and the Human Tumor Atlas Network, an effort to create atlases of a wide variety of cancer types in cellular and molecular detail.


University of California San Francisco (UCSF) scientists have designed a large-scale screen that efficiently identifies drugs that are potent cancer-killers when combined, but only weakly effective when used alone.

Using this technique, the researchers eradicated a devastating blood cancer and certain solid tumour cells by jointly administering drugs that are only partially effective when used as single-agent therapies. The effort, a cross-disciplinary collaboration between UCSF researchers, is described in a study published in the journal Cell Reports.

“Many cancers either fail to respond to a single targeted therapy or acquire resistance after initially responding. The notion that combining targeted therapies is a far more effective way to treat cancer than a single-drug approach has long existed. We wanted to perform screens with saturating coverage to understand exactly what combinations should be explored,” said UCSF’s Jeroen Roose, PhD, professor of anatomy and senior author of the new study.

Scientists have found that when they target two distinct circuits with two different drugs – each of which is inadequate on its own – the aggregate effect can be greater than the sum of its parts. However, figuring out which drugs can synergise to kill cancer remains a challenge.

To demonstrate the power of their screening system, the scientists searched for targeted therapies that could join forces to kill an aggressive blood cancer called T cell acute lymphoblastic leukaemia (T-ALL). Their hunt began with a drug that targets PI3K, an enzyme that promotes the growth of many cancers, including T-ALL. Though drugs that target PI3K already exist, the current crop of PI3K inhibitors can slow, but normally can’t kill, this type of cancer.

“Nearly 65 percent of T-ALL patients have hyperactive PI3K, but most patients will likely not be cured by single-drug treatments. We wanted to find drugs that would kill T-ALL when combined with a PI3K inhibitor,” said Roose, a member of the UCSF Helen Diller Family Comprehensive Cancer Center. To find those drugs, the researchers turned to RNA interference (RNAi) – a technique that allows scientists to massively reduce the activity of specific genes. The discovery of RNAi, which occurs naturally in all animals and plants, and is now widely used in research, was a major breakthrough that was recognised with the 2006 Nobel Prize in Physiology or Medicine.

“RNAi is sort of a magic bullet for targeting specific genes,” said Michael T. McManus, PhD, professor at the UCSF Diabetes Center and study co-author, who designed the screen with Roose. “Although there is a great deal of fascinating underlying biology that relates to RNAi, most scientists use it as a tool to ‘turn down the volume’ of a specific gene in a cell.”

The gene-editing tool CRISPR has made it possible to completely remove genes. But according to McManus, while eliminating a specific gene is the gold standard – an essential first step in determining its function in cells – at times, reducing a gene’s activity level using RNAi activity may be more desirable. This is especially true, he says, when researchers are seeking to mimic the effects of drugs, which often reduce the activity associated with a particular gene without completely eliminating it.

“When searching for cancer drugs, for example, RNAi may do a better job of approximating precision therapies, both of which only partially inhibit their biological targets,” McManus said. The researchers have also started exploring CRISPRi and CRISPRa – modified forms of CRISPR that inhibit or amplify the activity of target genes, respectively, without making cuts to the DNA – for these reasons.

Roose and McManus aren’t the first scientists to use RNAi to search for these kinds of combinatorial therapies. But earlier efforts were error-prone because those screens used RNAi libraries that were too small, Roose said. What sets the new study apart is the ultra-complex collection of short hairpin RNAs (shRNAs) that were used. These RNA fragments contain sequences that correspond to those found in messenger RNAs (mRNA) – the molecular arbiters of gene activity in the cell. When an shRNA finds an mRNA that contains a matching sequence, the two molecules bind together to initiate a process that destroys the mRNA and inhibits the activity of that gene. In total, the researchers targeted some 1,800 cancer-associated genes with approximately 55,000 shRNAs, or about 30 shRNAs per gene, “more than enough to eliminate false positives and false negatives,” Roose said.

The screen itself involved growing two different human T-ALL cell lines in the presence of PI3K inhibitors and then simultaneously administering shRNAs to find out which genes, when silenced in the presence of these drugs, killed the cancer. From this comprehensive screen, the researchers then focused on 10 genes whose activity, when curbed with precision medicines, was predicted to kill T-ALL cancer cells in combination with PI3K drugs. They tested these predictions and found that nine of the combined therapies could kill T-ALL – a feat that none of the drugs could achieve on its own. The researchers then tested the most effective of these synergistic drug combinations on mouse models of T-ALL and found that it could extend survival by 150 percent.

Recognising that discoveries made in blood cancers don’t always translate to solid tumours, the researchers also tested the predicted drug combinations on 28 solid tumour cell lines derived from human breast, colorectal, pancreatic and brain cancers. They found that even in these solid tumour cells, the combination therapies synergised to reduce the number of cancer cells by up to 20 percent over the course of the experiment.

“An important message from our work is that scientists can use leukaemia cells as a platform to find drug combinations that also work in solid tumours. Our screening platform is very generalisable,” Roose said.

Among the most surprising and promising of the results was that the researchers were able to find pairs of drugs that impeded cancer growth, but which had no effect on normal cells.

“Finding therapies that specifically target cancer without harming healthy tissue is the holy grail of cancer research,” Roose said. “This surprising result suggests that our method may aid in the discovery of this kind of cancer-specific precision medicine.”


In one of the largest studies of its kind, researchers used CRISPR technology to disrupt every gene in over 300 cancer models from 30 cancer types and discover thousands of key genes essential for cancer’s survival. The team, from the Wellcome Sanger Institute and Open Targets, then developed a new system to prioritise and rank 600 drug targets that show the most promise for development into treatments.

The results, published in Nature, accelerate the development of targeted cancer treatments and bring researchers one step closer to producing the Cancer Dependency Map, a detailed rulebook of precision cancer treatments to help more patients receive effective therapies.

Scientists and pharmaceutical companies are exploring new targeted therapies that selectively kill cancer cells, leaving healthy tissue unharmed. Currently, producing new effective treatments is very difficult; it costs approximately $1–2 billion to develop a single drug, but around 90 percent of drugs fail during development. Selecting a good drug target at the beginning of the process can therefore be seen as the most important part of drug discovery.

Researchers at the Wellcome Sanger Institute, GSK, EMBL-EBI, Open Targets and their collaborators have conducted one of the largest CRISPR screens of cancer genes to date, disrupting nearly 20,000 genes in over 300 cancer models from 30 cancer types to uncover which genes are critical for cancer survival.

The team focused on common cancers, such as lung, colon and breast, and cancers of particular unmet clinical need, such as lung, ovarian and pancreatic, where new treatments are urgently needed.

Scientists identified several thousand key cancer genes and developed a prioritisation system to narrow down the list to approximately 600 genes that showed the most promise for drug development.

A top-scoring target present in multiple different cancer types was Werner syndrome RecQ helicase (WRN). The team found that cancer cells with a faulty DNA repair pathway, known as microsatellite unstable cancers, require WRN for survival. Microsatellite instability occurs in many different cancer types, including 15percent of colon and 28percent of stomach cancers. The new identification of WRN as a promising drug target offers an exciting opportunity to develop the first cancer treatments to target WRN.

Dr Kosuke Yusa, co-lead author previously from the Wellcome Sanger Institute and Open Targets, now based at the Institute of Frontier Life and Medical Sciences, Kyoto University, said: “CRISPR is an incredibly powerful tool that enables us to do science at a scale and with a precision that we couldn’t do five years ago. With CRISPR we have discovered a very exciting opportunity to develop new drugs targeting cancers.”

Dr Francesco Iorio, co-first author from the Wellcome Sanger Institute and Open Targets, said: “To give a new drug the best chance of succeeding in the very final phases of clinical trials, it is crucial to select the best and most promising drug target at the beginning of the drug development process. For the first time, in a data-driven way, we provide guidance at a genome-scale on which new therapeutic targets should be put forward for the development of new anti-cancer drugs.”

The collaboration between researchers at Sanger, EMBL-EBI and GSK, the Open Targets partners, bolster the translation of these research results into new treatments.

The datasets produced in this new study lay the foundations for producing the Cancer Dependency Map, a detailed rulebook for the precision treatment of cancer.


Vaccination with as few as four tumour antigens generated antigen-specific responses, reduced intestinal tumours, and improved survival in a mouse model of Lynch syndrome, suggesting that it may be possible to develop a cancer preventive vaccine for patients with Lynch syndrome, according to data presented at the AACR Annual Meeting 2019 last week.

“Lynch syndrome is an inherited condition that affects about one in every 280 individuals in the United States,” said Steven M. Lipkin, MD, PhD, the Gladys and Roland Harriman Professor of Medicine, professor of medicine in the Division of Gastroenterology and Hepatology, and vice chair for research in the Weill Department of Medicine at Weill Cornell Medicine in New York; and a geneticist at NewYork-Presbyterian/Weill Cornell Medical Center. “People with Lynch syndrome have a 70–80 percent lifetime risk of colorectal cancer, as well as an increased risk for other types of cancer, including small intestine, stomach, endometrial, bladder, and ovarian cancers.

“Currently, frequent screening to detect pre-cancers and early-stage cancer is the main approach used to prevent cancer in people with Lynch syndrome, although some people have risk-reducing surgeries and some take aspirin for colorectal cancer prevention,” continued Lipkin, who is also a member of the Sandra and Edward Meyer Cancer Center and the Caryl and Israel Englander Institute for Precision Medicine at Weill Cornell Medicine. “We are extremely encouraged by our pre-clinical data, which suggest that rationally designed cancer vaccines may prevent some cancers associated with Lynch syndrome. We are in the process of designing a clinical trial to test this hypothesis.”

The genetic mutations that cause Lynch syndrome prevent the proper repair of damaged DNA, leading to the accumulation of mutations in certain parts of the genome called coding microsatellites, explained Lipkin. The coding microsatellite mutations generate novel or modified proteins called neoantigens, which can be recognised by the patient’s immune system but usually do not yield a sufficiently robust immune response to prevent cancers from developing, he added.

In this study, Lipkin and colleagues investigated whether vaccinating mice with Lynch syndrome-associated neoantigens could stimulate a robust immune response that would have anti-tumour activity.

One of the first steps the researchers took was to analyse intestinal tumours from Lynch syndrome mice for mutations in the coding microsatellites. They identified 13 coding microsatellites that had at least one mutation that occurred in 15 percent or more of the tumours.

Further analysis was conducted to determine which mutations might generate neoantigens and what the peptide sequences of these neoantigens were. The team then tested how effective the 10 most promising neoantigens were at inducing an immune response in mice. They found four of the neoantigens generated from coding microsatellite mutations induced robust neoantigen-specific immune responses.

Vaccination of Lynch syndrome mice with the four neoantigens induced robust neoantigen-specific immune responses. It also significantly reduced intestinal tumour burden and improved survival compared with non-vaccinated Lynch syndrome mice. In non-vaccinated Lynch syndrome mice, the median intestinal tumour burden was 61mg and overall survival was 241 days, compared with 31mg and 380 days, respectively, in vaccinated Lynch syndrome mice.

Combining vaccination and administration of the nonsteroidal anti-inflammatory drug naproxen significantly improved overall survival for the Lynch syndrome mice compared with vaccination alone; in mice receiving the combination treatment, overall survival was 541 days versus 380 days in mice receiving only the vaccine.

“Our preclinical data are very exciting because they provide strong support for continuing the investigation and development of immunoprevention strategies for patients with Lynch syndrome,” said Lipkin.


A worldwide collaboration led by researchers at Sanford Burnham Prebys has demonstrated a causal link between the gut microbiome and the immune system’s ability to fight cancer.

Together, the researchers identified a cocktail of 11 bacterial strains that activated the immune system and slowed the growth of melanoma in mice. The study also points to the role of unfolded protein response (UPR), a cellular signalling pathway that maintains protein health (homeostasis).

Reduced UPR was seen in melanoma patients who are responsive to immune checkpoint therapy, revealing potential markers for patient stratification.

“The investigators have pinpointed the UPR as an important link between the gut microbiota and anti-tumour immunity. Given previous work indicating a causal role for the host microbiota in the efficacy of checkpoint blockade immunotherapy, this additional mechanistic insight should help select patients who will respond to treatment and also help to guide new therapeutic development.” says Thomas Gajewski, the AbbVie Foundation Professor of Cancer Immunotherapy at the University of Chicago Medicine.

Although immune checkpoint therapies have significantly improved patient survival rates, metastatic melanoma remains the deadliest form of skin cancer, according to the American Cancer Society. Even when used as part of combination therapy, immune checkpoint inhibitors only benefit about half of patients, and these responses may involve autoimmune-related side effects, limited durability (the length of time a patient responds to treatment) and, at times, resistance to therapy.

Accumulating evidence supports the role of the gut microbiome in effective immune therapy: Antibiotics and select probiotics reduce treatment efficacy, while certain bacterial strains enhance efficacy. This study sheds new light on these observations.

“Our study establishes a formal link between the microbiome and anti-tumour immunity and points to the role of the UPR in this process, answering a long-sought question for the field,” says Ze’ev Ronai, senior author of the study and a professor at Sanford Burnham Prebys’ NCI-designated Cancer Center. “These results also identify a collection of bacterial strains that could turn on anti-tumour immunity and biomarkers that could be used to stratify people with melanoma for treatment with select checkpoint inhibitors.”

As part of this work, Ronai and his team are studying a genetic mouse model that lacks the gene for RING finger protein 5 (RNF5), a ubiquitin ligase that helps remove inappropriately folded or damaged proteins. While these molecular traits are critical for the current study, the mice don’t show any outward signs of disease.

“We call them the ‘boring mice’ because they don’t have a notable phenotype,” says Ronai. However, the RNF5-lacking mice were able to inhibit the growth of melanoma tumours, provided they had an intact immune system and gut microbiome. Treating these mice with a cocktail of antibiotics or housing the mice with their regular (wildtype) littermates abolished the anti-tumour immunity phenotype and consequently, tumour rejection indicating the important role of the gut microbiome in anti-tumour immunity. Mapping the immune components engaged in the process revealed several immune system components, including Toll-like receptors and select dendritic cells, within the gut intestinal environment. Reduced UPR was commonly identified in immune and intestinal epithelial cells and was sufficient for immune cell activation. Reduced UPR signalling was also associated with the altered gut microbiomes seen in the mice.

“We believe this research applies to another fundamental question pertaining to the balance between anti-tumour immunity and autoimmunity,” says Ronai. “Because mice that lack RNF5 are also prone to developing gut inflammation – a side effect seen for certain immune checkpoint therapies – we can exploit this powerful model to study how we may tilt the balance between autoimmunity and anti-tumour immunity, which could help more people benefit from these remarkable therapies.”

The study was published in Nature Communications (PDF).


Researchers at the RIKEN Center for Sustainable Resource Science (CSRS) in Japan have developed a new computational mass-spectrometry system for identifying metabolomes – entire sets of metabolites for different living organisms.

When the new method was tested on select tissues from 12 plant species, it was able to note over 1,000 metabolites. Among them were dozens that had never been found before, including those with antibiotic and anti-cancer potential.

In addition to facilitating the screening of plant-specialised metabolomes, the new process could speed up the discovery of natural products that could be used in medicines, according to the team.

Hiroshi Tsugawa, one of the lead researchers, said: “I believe that computationally decoding metabolomic mass spectrometry data is linked to a deeper understanding of all metabolisms. Our next goal is to improve this methodology to facilitate global identification of human and microbiota metabolomes as well. Newly found metabolites can then be further investigated via genomics, transcriptomics, and proteomics.”

The common pain reliever aspirin (acetylsalicylic acid) was first made in the 19th century and is famously derived from willow bark extract. After a new method of synthesis was discovered and used for almost 70 years, scientists were finally able to understand how it works. This was a long historical process.

There are millions of plant species and each has its own metabolome – the set of all products of the plant’s metabolism. Currently, we only know about 5 percent of all these natural products. Although mass spectrometry can identify plant metabolites, it only works for determining if a sample contains a given molecule.

Computational mass spectrometry is a growing research field that focuses on finding previously unknown metabolites and predicting their functions. The field has established metabolome databases and repositories, which facilitate global identification of human, plant, and microbiota metabolomes.

Led by Hiroshi Tsugawa and Kazuki Saito, a team at CSRS has spent several years developing a system that can quickly identify large numbers of plant metabolites, including those that have not been identified before.

As Tsugawa explains, “while no software can comprehensively identify all the metabolites in a living organism, our program incorporates new techniques in computational mass spectrometry and provides 10 times the coverage of previous methods.” In tests, while mass spectrometry-based methods only noted about 100 metabolites, the team’s new system was able to find more than 1,000.

The new computational technique relies on new algorithms that compare the mass spectrometry outputs from plants that are labeled with carbon-13 with those that are not. The algorithms can predict the molecular formula of the metabolites and classify them by type. They can also predict the substructure of unknown metabolites, and based on similarities in structure, link them to known metabolites, which can help predict their functions.

In particular, the system was able to characterise a class of antibiotics (benzoxazinoids) in rice and maize as well as a class with anti-inflammatory and antibacterial properties (glycoalkaloids) in the common onion, tomato, and potato. It was also able to identify two classes of anti-cancer metabolites, one (triterpene saponins) in soy beans and liquorice, and the other (beta-carboline alkaloid) in a plant from the coffee family.

Scientists home in on microRNA processing for novel cancer therapies

More than a decade of research on the mda-7/IL-24 gene has shown that it helps to suppress a majority of cancer types, and now scientists are focusing on how the gene drives this process by influencing microRNAs.

Published in March in the journal Proceedings of the National Academy of Sciences, the findings could potentially have implications beyond cancer for a variety of cardiovascular and neurodegenerative diseases caused by the same microRNA-driven processes.

The study was led by Paul B. Fisher, M.Ph., Ph.D., F.N.A.I., Thelma Newmeyer Corman Endowed Chair in Cancer Research and member of the Cancer Molecular Genetics research program at Virginia Commonwealth University Massey Cancer Center, chairman of the Department of Human and Molecular Genetics at VCU School of Medicine and director of the VCU Institute of Molecular Medicine (VIMM).

The mda-7/IL-24 gene was originally discovered by Fisher. He and his colleagues have since published a number of studies detailing how the gene can suppress cancer by directly influencing two important mediators of cell death known as apoptosis and toxic autophagy. They have also been developing mda-7/IL-24 viral gene therapies, purified protein treatments and T-cell-delivered therapies that take advantage of these processes to selectively kill cancer cells.

MicroRNAs play decisive roles in a variety of diseases, including cancer. This study shows for the first time how mda-7/IL-24 influences an enzyme critical to microRNA processing, and it provides exciting clues as to how this process could be targeted therapeutically,” says Fisher.

The researchers showed that mda-7/IL-24 reduces the expression of an enzyme called DICER, and this effect occurs only in cancer cells. DICER works to process microRNAs for specific cellular functions. In experiments involving prostate, breast and brain cancer cell lines and mouse models, overexpression of DICER was shown to rescue cancer cells from mda-7/IL-24-mediated cell death.

Microphthalmia-associated transcription factor (MITF) was found to be a key mediator in this process. MITF regulates cellular responses to reactive oxygen species (ROS), a natural byproduct of the normal metabolism of oxygen and an important component in cell signaling. In times of cellular stress, ROS levels can increase dramatically and contribute to the development of disease. The scientists showed for the first time that mda-7/IL-24 down-regulates MITF, which, in turn, down-regulates DICER, the target of MITF.

Previous experiments showed a potent bystander effect where mda-7/IL-24 not only killed cancer cells at the primary tumour site but also in distant secondary tumours not directly targeted by the therapy. The bystander effect is mediated, at least in part, by the potent immune activating and anti-growth properties of mda-7/IL-24. These findings help explain why this bystander effect occurs.

“This is an exciting and previously unknown link between mda-7/IL-24 and ROS/MITF/DICER that we plan to continue exploring,” says Fisher. “This research may open up new therapeutic targets, and monitoring the levels of these components could provide important biomarkers to help inform the effectiveness of mda-7/IL-24-based therapies.”


Scientists have developed a microfluidic device that is able to isolate individual cancer cells from patient blood samples.

Researchers at the University of Illinois at Chicago and Queensland University of Technology of Australia developed the device that can be used to separate the various cell types found in blood by size.

“This new microfluidics chip lets us separate cancer cells from whole blood or minimally-diluted blood,” said Dr Ian Papautsky, the Richard and Loan Hill Professor of Bioengineering in the UIC College of Engineering and corresponding author on the paper.

“While devices for detecting cancer cells circulating in the blood are becoming available, most are relatively expensive and are out of reach of many research labs or hospitals. Our device is cheap, and doesn’t require much specimen preparation or dilution, making it fast and easy to use.”

The researchers mentioned how their device could enable rapid, cheap liquid biopsies to help the detection of cancer, and may even aid the development of targeted treatment.

 The ability of the device to isolate cancer cells is a crucial step, and would eliminate the discomfort and cost of tissue biopsies. Liquid biopsy could also track to efficacy of chemotherapy over time, and even to detect cancer in organs.

The isolation of these cancer cells is extremely difficult, since they are present in tiny quantities. For many cancers, circulating cancer cells are present as levels as low as one per one billion blood cells.

“A 7.5-milliliter tube of blood, which is a typical volume for a blood draw, might have ten cancer cells and 35-40 billion blood cells,” said Prof Papautsky. “So we are really looking for a needle in a haystack.”

“Using size differences to separate cell types within a fluid is much easier than affinity separation which uses ‘sticky’ tags that capture the right cell type as it goes by. Affinity separation also requires a lot of advanced purification work which size separation techniques don’t need.”

The developed device works through the phenomena of inertial migration and shear-induced diffusion to separate cancer cells from blood as it passes through ‘microchannels’ formed in plastic.

“We are still investigating the physics behind these phenomena and their interplay in the device, but it separates cells based on tiny differences in size which dictate the cell’s attraction to various locations within a column of liquid as it moves.”

After ‘spiking’ healthy blood with non-small cell lung cancer cells, the device was able to recover 93 percent of the cancer cells. When run on actual samples from patients with non-small cell lung cancer, the microfluidic device was able to separate cancer cells from six of the eight samples.

The study was published in the journal Microsystems and Nanoengineering.


A mechanism for activating the immune system against cancer cells allows immune cells to detect and destroy cancer cells better than before.

The study was led by Professor Nick Haining, at Harvard Medical School, and was co-authored by Professor Erez Levanon, doctoral student Ilana Buchumansky, of the Mina and Everard Goodman Faculty of Life Sciences at Bar-Ilan University, and an international team.

The focus of the study was to develop a mechanism that routinely serves the cell by marking human virus-like genes in order to avoid identifying them as viruses. 

Prof Levanon, together with the Harvard team, discovered during the study that when inhibiting this mechanism, the immune system can be harnessed to fight cancer cells in a particularly efficient manner, and also more effectively in both lung cancer and melanoma.

“We found that if the mechanism is blocked, the immune system is much more sensitive. When the mechanism is deactivated, the immune system becomes much more aggressive against the tumor cells,” said Prof Levanon.

In recent years, a new generation of cancer drugs has been developed which blocks proteins that inhibit immune activity against malignant tumors. These drugs have shown remarkably poisitve success in several tumor types, in some.

This year’s Nobel Prize in Medicine was awarded to James Allison and Tasuku Honjo, who discovered the key genes of this mechanism.

Despite this achievement, the current generation of drugs helps only a small number of patients, while most of the drugs fail to cause the immune system to attack the tumor.

The research team hope that the new discovery will allow enhanced activity of the immune system to attack cancer cells. A number of companies have already begun research to screen for drugs that will operate on the basis of this discovery.

The study was published in the journal Nature.