This minimally invasive technique, called Polarization Gating Spectroscopy, will now be tested in a much larger international clinical trial led by the Mayo Clinic researchers. The preliminary study suggests it may be possible, one day, to use a less invasive endoscope to screen patients for early development of pancreatic cancer.

The pancreas is notoriously hard to reach and see due to its very deep location in the abdomen, surrounded by intestines. The study investigators theorized that there may be changes in the nearby “normal appearing” tissue of the small intestine which is much more accessible.

“No one ever thought you could detect pancreatic cancer in an area that is somewhat remote from the pancreas, but this study suggests it may be possible,” says Dr. Michael Wallace, chairman of the Division of Gastroenterology at Mayo Clinic in Florida. “Although results are still preliminary, the concept of detection field effects of nearby cancers holds great promise for possible early detection of pancreatic cancer.”

In this study, the Mayo Clinic physicians tested a light probe developed by their long-time collaborators at Northwestern University.

The light, attached to a small fiber-optic probe known as an endoscope, measures the amount of oxygenated blood as well as the size of blood vessels in tissue near the duct where the pancreas joins the small intestine. Because a growing tumor requires a heightened supply of blood, normal tissue in the vicinity of the cancer reveals evidence of enlarged blood vessels and changes in the amount of oxygen within the blood.

Such “field effects” from cancer can be measured in other areas of the GI tract, says Dr. Wallace. “With this technology, others studies have shown that cancerous polyps can be detected more than 11 inches from the polyp itself. Early studies are evaluating if esophageal cancers can also be detected remotely,” he says.

The probe acts “a bit like a metal detector that beeps faster and louder as you get close to cancer,” he says. The researchers are measuring within six to 10 inches of the pancreas in the small intestine immediately next to the pancreas.

Dr. Wallace and his team tested the probe on 10 patients who were later determined to have pancreatic cancer, and on nine participants who did not have pancreatic cancer.

They found that testing both measures — blood vessel diameter and blood oxygenation — detected all 10 pancreatic cancers. But the probe was less precise (63 percent accurate) in determining which of the healthy volunteers did not have pancreatic cancer.

“There is room for improvement in this instrument, and our group is working on that,” he says. “If the studies confirm the early results, it would make the pancreas accessible to a much simpler upper endoscope and that would be a real advance in the treatment of pancreatic cancer.”

Patients now often undergo an endoscopic examination of the upper intestine to search for the cause of heartburn or stomach pain, Dr. Wallace says. An endoscopic probe could be easily outfitted to explore for evidence of pancreatic cancer in patients at heightened risk, he says.

Mihir Patel, M.D., a gastroenterologist who worked with Dr. Wallace on the study, says that despite of intense research, we haven’t been successful in significantly improving the overall survival associated with pancreatic cancer in the past several decades. That’s because we haven’t been able to detect the cancer early enough. Developing a technique to screen the patients and detect pancreatic cancer at an early stage would be a potential breakthrough. In preliminary data, this technology has shown to hold similar potential.

“This really is a broad-based, multi-disciplinary team effort,” Kenny said. “We’ve assembled a team of first-class scientists at Scripps Florida with all the experience necessary to develop novel therapeutics for the treatment of tobacco abuse.”

Others involved in the study are Michael Cameron, Theodore Kamenecka, and Patricia McDonald of The Translational Research Institute on the Scripps Florida campus.

Tobacco smoking is a global scourge, killing more than 5 million people each year worldwide, according to the World Health Organization. It is estimated that if current trends continue, by 2020 smoking will become the largest single health problem worldwide. The World Bank estimates that in high-income countries, smoking-related healthcare accounts for between 6 and 15 percent of all healthcare costs, some $160 billion annually.

Nicotine addiction is notoriously hard to break. Even with the most effective smoking-cessation agents available, more than 80 percent of smokers who quit or attempt to quit will relapse.

To combat these dismal statistics, the study is focused on an entirely new mechanism to help smokers break the habit.

That mechanism is a receptor for a specific neuropeptide (short chain of amino acids found in nerve tissue) that, when blocked, significantly decreases the desire for nicotine in animal models.

The neuropeptide, known as hypocretin-1 or orexin A, initiates a key signaling cascade that maintains tobacco addiction in human smokers. In a 2008 study in the Proceedings of the National Academy of Sciences, Kenny and colleagues showed that blocking hypocretin-1 receptors not only decreased nicotine use in animal models, but also abolished the stimulatory effects of nicotine on brain reward circuitries. These results demonstrated that hypocretin-1 plays a major role in driving the desire for more nicotine.

These findings also highlighted the importance of hypocretin-1 receptors in a region of the brain called the insula, a walnut size part of the frontal lobe. While all mammals have insula regions that sense the body’s internal physiological state and direct responses to maintain homeostasis, this region has also been implicated in cravings. In one study, it was reported that smokers who sustained damage to the insula lost the desire to smoke, an insight that revealed the insula as key for sustaining the tobacco habit in smokers.

Biovest based its decision to pursue EU marketing approval on pre-filing clinical advisory meetings with EU-member national regulatory agencies. Under the EMA centralized procedure, Biovest will simultaneously seek approval for BiovaxID for all EU-member countries.

Samuel S. Duffey, Esq., Biovest’s President & CEO, stated, “Biovest’s EU regulatory strategy focused on conducting pre-filing clinical meetings with national regulatory agencies to obtain scientific advice regarding our BiovaxID clinical data and to facilitate a more predictable marketing approval process in the European Union. Today’s announcement confirms that pre-filing meetings have been conducted in Europe, and the Company intends to file a marketing application with the EMA. This is a major regulatory milestone, and it builds on Biovest’s recently announced plans to seek marketing approval in Canada following a pre-filing meeting with Health Canada. We next look forward to meetings with the FDA to define the path to U.S. registration as well.” Bi0vest is a majority-owned subsidiary of Accentia Biopharmaceuticals, Inc.

Ravi K. Amaravadi, MD, assistant professor of Medicine, and colleagues showed previously that an old malaria drug, hydroxychloroquine, reduces autophagy in cancer cells and makes them more likely to die when exposed to chemotherapy. The strategy is currently being tested in clinical trials, and preliminary results are promising. The catch, though, is that it’s not always possible to give patients a high enough dose of hydroxychloroquine to have an effect on their tumor cells.

Amaravadi teamed up with Jeffrey Winkler, PhD, the Merriam Professor of Chemistry, to design a series of more potent versions of chloroquine. They describe the design, chemical synthesis, and biological evaluation of a highly effective, new compound called Lys05, in the early edition of the Proceedings of the National Academy of Sciences this week. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency

Unlike hydroxychloroquine, which has little impact on tumor cells when used as a single agent, the new drug, called Lys05, slows tumor growth in animal models even in the absence of other anti-tumor therapies. What’s more, the Lys05 dose that is toxic to cancer cells, which are addicted to recycling and rely on it much more heavily than healthy cells, has little or no effect on healthy cells.

“We see that Lys05 has anti-tumor activity at doses that are non-toxic for the animals,” Amaravadi says. “This single-agent anti-tumor activity suggests this drug, or its derivative, may be even more effective in patients than hydroxychloroquine.” Remarkably, however, when the investigators increase the dose of Lys05, some animals develop symptoms that mimic a known genetic deficiency in an autophagy gene, ATG16L1, which affects some patients with Crohn’s disease . That similarity — technically called a phenocopy — clearly shows that Lys05 works by interfering with the recycling system in cells.

Lys05, and its companion compound Lys01, aren’t quite ready for testing in patients, according to Amaravadi. Before that can happen, the molecules need to be optimized and undergo more toxicity testing in animals. Amaravadi and Winkler hope to team up with an industry partner for that portion of the project.

In the meantime, though, Amaravadi says the work illustrates just how important autophagy is to cancer cells, and provides an important new step for future therapies.

Published in Nature Medicine, Monoclonal TCR-redirected tumor cell killing examined the potential of molecules on the surface of anti-cancer killer T cells, known as T cell receptors (TCRs) to be used to treat cancers for which few disease-specific targets are available.

The Immunocore team engineered a range of TCRs to bind very tightly to cancer cells and equipped them with the ability to activate non-cancer specific T cells. This new class of drug, named ‘ImmTACs’ (Immune Mobilising mTCR against Cancer), can be used to ‘hi-jack’ the body’s existing T cells that normally kill viruses and redirect them to kill cancer cells instead.

The team included Nat Liddy and Katy Adams, Immunocore employees and PhD students at Cardiff University, as well as Professors Andy Sewell and David Price, School of Medicine.

“With Immuncore’s novel ImmTAC drugs we found we could effectively target cancer cells and mark them for destruction by the killer T cells that might normally fight common infections” said Liddy

“Our initial studies and findings show that administration of ImmTAC could, potentially, result in the regression of established tumors.”

Recent advances have enabled molecular targeting of disease using immune molecules called antigen receptors. There are two main classes of antigen receptor: antibodies and T cell receptors.

Therapeutic application of antibodies has been a huge medical success over the last decade and over 40% of the new drugs on the market in 2011 were based on these molecules.

Exploitation of T cell receptors (TCRs) has so far lagged behind, but research led by Immunocore Ltd, with help from Cardiff University’s Institute of Infection and Immunity, is set to close the gap and open up an entirely new field of medical treatments.

“T cell receptors have advantages over antibodies as these molecules can see inside cells and tell if they are abnormal” said Professor Andy Sewell. “Similar technology based around antibodies has shown great promise in clinical trials. This new TCR-based research technology extends this potential as it could possibly be applied to any form of cancer.”

The most advanced of Immunocore’s ImmTACs, a drug called IMCgp100, is already in clinical trials in the UK and US for the treatment of melanoma. A second oncology ImmTAC, IMCmage1, is set to enter the clinic in both countries later this year and is applicable to the treatment of a large number of poorly served cancer indications.

James Noble, Immunocore’s CEO, said: “The power of this new technology lies in its ability to be used for a host of cancers that are currently very difficult to treat. We look forward to building on the emerging clinical data and generating a robust pipeline of products over the coming years”.

Using an automated, high-volume screening technique, researchers at Washington University School of Medicine in St. Louis have identified a cancer drug that enhances an important natural response to viral infection in human cells.

“Over many years of research, we have developed a good understanding of the human body’s own mechanisms to fight viruses,” says the study’s first author Dhara Patel, PhD, a postdoctoral research scholar at Washington University. “Instead of targeting the virus itself, which most current antiviral drugs do, we have designed a strategy to look for chemical compounds that will enhance this innate antiviral system.”

Of the 2,240 compounds researchers tested, 64 showed increased activity in the cells’ interferon signaling pathway, an important player in the body’s response to viruses. The 64 compounds included many different classes of drugs treating conditions as diverse as depression, high blood pressure and ulcers. But the one that stood out is idarubicin, a cancer drug commonly prescribed to treat leukemia, lymphoma and breast cancer. Even at low doses, idarubicin significantly ramps up the interferon signaling system.

In treating cancer, idarubicin stops cells from dividing by blocking a protein that unwinds DNA. As long as DNA remains tightly packed, it can’t be copied. And if DNA can’t be copied, a cell can’t divide. Interestingly, though, the researchers showed that idarubicin’s antiviral effects are totally unrelated to what makes it a good cancer drug.

“We tested other cancer drugs that work the same way as idarubicin but have very different structures,” Patel says. “Although they act the same way that idarubicin does in cancer cells, they had no effect on the interferon system.”

Like many cancer drugs, idarubicin has toxic side effects, so it is unlikely to ever be prescribed for patients fighting viral infections. But, its identification demonstrates that the new strategy works.

“While idarubicin is not something you would give to a patient who has the flu, we are continuing to screen more drugs,” Patel says. “We’re starting to find compounds from different drug classes that are not so toxic and that have similar properties in enhancing interferon signaling. We’re still validating them, but we’re very excited about what we’re finding.”

Traditionally, techniques for drug discovery involve trying to enhance or inhibit a very specific interaction. To treat a particular disease, scientists might try to disable a harmful protein, or replace a missing one, for example. But such approaches assume that altering a specific interaction of interest will result in the desired effect.
“I think our technique accepts the fact that we don’t understand everything that’s going on in the cell,” Patel says. “Instead of looking at one particular interaction, we measure the downstream effects.”

She compares it to driving a car and trying to make it go faster.

“Traditionally, we would pick a specific part — a part of the car that we think is responsible for speed — and then test compounds that alter the part in a way that we think will make the car go faster,” she says. “With our approach, we don’t assume we know what is responsible for speed. Instead, we take entire cars, treat them with many different compounds, and just see which ones go faster.”

Patel says this screening technique is unusual because it can identify drugs that enhance the body’s own immune response to a broad range of viruses, unlike a vaccine, which only protects against a specific virus.

The method has also shed light on how some compounds with known antiviral properties actually fight viruses. In addition to cancer drugs, antidepressants and blood pressure medications, the initial 64 drugs they identified with increased interferon activity included some known antiviral drugs.

“We already knew some of these compounds had antiviral properties, we just didn’t know why,” Patel says. “Now we’re starting to find out how they actually work.”

“The partnership with IHT will offer OPKO a unique opportunity for our kallikrein panel in select initial markets,” said Phillip Frost, M.D., Chairman and CEO of OPKO Health. “We believe this technology will enable IHT to provide the patients they serve with better and more efficient healthcare, while lowering overall costs. We hope eventually that this panel will become the standard of care in prostate cancer screening.”

The OPKO panel represents the culmination of a decade of research by scientists in Europe and the U.S. and has been demonstrated in over 10,000 patients to predict the probability of cancer-positive biopsy in men suspect for prostate cancer. Studies have shown use of the panel could eliminate a significant amount of unnecessary prostate biopsies, demonstrating a reduction of over 50%.

International Health Technology, through close cooperation with some of the largest private hospitals chains in the UK and abroad, has access to world class private facilities and specialists to provide testing services for corporate clients in the private sector.

According to Alexander R. A. Anderson, Ph.D., chair of the IMO, mathematical models can be useful tools for the study of cancer progression as related to understandings of tumor ecology.

“Cancer is a complex disease driven by interactions between tumor cells and the tumor’s microenvironment,” Anderson said. “By developing mathematical models that describe how tumors grow and respond to changes in their surroundings (such as treatment), we can better understand how an individual patient might respond to a whole suite of different therapies.”

Robert Gillies, Ph.D., chair of imaging and metabolism at Moffitt, is working closely with Anderson and Robert Gatenby, M.D., chair of Diagnostic Imaging. They say it is important to pair tumor imaging with mathematical model building.

“Imaging is a key to validate mathematical modeling,” Gillies said. “Because imaging can be conducted over time, it affords us a good look at the actively changing systems in tumors that are predicted by the models.”

For Gatenby, because cancer is an evolving, always changing nonlinear system, it must be monitored over time and space.

“Imaging noninvasively captures tumor changes, and the mathematical models, which are much more rigorous than language, can then be used in cancer research,” Gatenby said.

Clinical imaging and mathematical modeling combined will afford clinicians a valuable predictive tool. One tool will be familiar. Just as meteorologists develop “spaghetti models” from satellite images to predict the myriad possible paths of hurricanes, Anderson said, they will be able to generate similar models to inform clinicians about a patient’s risk, which treatments may be best and whether recurrence is possible.

“By incorporating specific information about a patient, such as the size of their tumor, the treatments they have had, the organ that the cancer is growing in, we can predict forward in time how the tumor will grow, shrink, and respond to different combinations of therapies. By the results of imaging, biological experiments and mathematical models, we are leading the world in patient-specific medicine,” Anderson said.

Mathematical models generated by IMO researchers are already finding clinical uses.
Fibroblasts contribute to melanoma tumor growth

“We used an integrated mathematical and experimental approach to investigate whether melanoma cells recruit, activate and stimulate fibroblasts to deposit certain proteins known to be pro-survival for melanoma cells,” Anderson said.

Fibroblasts, the most common connective tissue functioning in the extra cellular matrix, were known to be activated by and drawn to cancer cells. When they investigated the relationship between fibroblasts and tumors using mathematical models, Anderson and colleagues found that fibroblasts have direct effects on melanoma tumor behavior, including aiding tumor growth and tumor drug resistance. They published their findings in Molecular Pharmaceutics.
Deadly glioblastomas better understood through mathematical models

IMO researchers and colleagues also developed mathematical models for investigating the progression of glioma, an aggressive and fatal form of brain cancer. The mathematical models augment imaging and histologic grading of gliomas, graded on their blood vessel growth patterns (an angiogenic feature) and incorporating the tumor’s cellular and microenvironmental changes.

When the researchers observed a disparity between grading schemes and tumor activity observed through imaging, they developed a mathematical model based on changes in cell appearance, proliferation and invasion rates. The new model improved predictive and prognostic ability.

“Being able to identify and predict patterns of dynamic changes in glioma histology as distinct from cellular changes in appearance and proliferation may provide a powerful clinical tool,” Anderson said.

They published this study in a recent issue of Cancer Research.
IMO gets $3 million from NIH to develop mathematical models of prostate cancer

As 2011 closed out, a group led by Anderson and colleagues landed a $3 million grant from the National Institutes of Health to create mathematical models to predict prostate cancer aggressiveness. It is well known that some prostate cancers are slow growing while others are aggressive. To be able to discriminate between them is critical if we want to treat only the aggressive ones, and there are potentially many patients that might not need treatment if we can make this distinction.

To construct the models, researchers will use tissue samples donated from prostate cancer patients to capture signaling mechanisms in tumor cells and understand how the different signaling in tumor cells alters how they behave. Using this data they will be able to identify and model the characteristics of aggressive prostate cancers. A second key step will be to clinically validate these newly constructed mathematical models, against an independent group of patients, as predictors of aggressive prostate cancers.

The University of California, Santa Cruz, has now completed a first step in building this infrastructure, said UC Santa Cruz bioinformatics expert David Haussler. Haussler’s team has established the Cancer Genomics Hub (CGHub), a large-scale data repository and user portal for the National Cancer Institute’s cancer genome research programs. CGHub’s initial “beta” release is providing cancer researchers with efficient access to a large and rapidly growing store of valuable biomedical data. The project is funded by the National Cancer Institute (NCI) through a $10.3 million subcontract with SAIC-Frederick Inc., the prime contractor for the Frederick National Laboratory for Cancer Research.

In personalized care, doctors design treatments to target specific genetic changes found in a patient’s cancer cells. Researchers are trying to catalog all the genetic abnormalities found in different types of cancers and find connections between specific genetic changes and how patients respond to different treatments. The scale and complexity of the information being gathered creates a critical challenge in the area of data management.

Although recent studies using genetically targeted treatments have shown promising results, much more research is needed to enable their widespread use, Haussler said. “There won’t be one magic bullet, because cancer is not one disease, or even 100 diseases. Every instance of cancer is different. We have to improve our understanding of the molecular biology of cancer and develop computer algorithms so that we can analyze the genetic changes in each individual patient. It will take time. But with cancer genomics, we will eventually know our enemy completely.”

Haussler’s team assembled the first draft of the human genome sequence in 2000 and created and maintains the UCSC Genome Browser, a web-based tool that is used extensively in biomedical research and serves as the platform for several large-scale genomics projects. His group’s contributions to cancer genomics research include creation of a Cancer Genomics Browser for analyzing data from large-scale cancer studies.

Haussler’s group built CGHub to support all three major NCI cancer genome sequencing programs: The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and the Cancer Genome Characterization Initiative (CGCI). TCGA is a collaborative effort led by NCI and the National Human Genome Research Institute to map the genomic changes that occur in at least 20 major types and subtypes of adult cancer. The TARGET program is a related effort focusing on the five most common childhood cancers, and the CGCI makes available genomic data from HIV-associated cancers and certain lymphoid and childhood cancers.

These programs are laying the foundation for personalized cancer care by creating a database that scientists around the world can use to connect specific genomic changes with clinical outcomes. Haussler’s group has been closely involved in data analysis for TCGA.

“TCGA is allowing us for the first time to look at cancer in full molecular detail,” Haussler said. “Cancer is a disease caused by disruption of DNA molecules within the cell. When life starts, every cell in the body has the same DNA. In the course of a person’s lifetime, however, some cells may accumulate changes in their DNA that cause them to go rogue and multiply without control, creating the disease we call cancer. For the first time now, we are able to look into an individual patient’s cancer cells and see all the genetic disruptions, among which are the molecular drivers of that person’s cancer.”

There are currently only a few situations in which doctors can prescribe a treatment plan based on the specific genetic mutations in a patient’s cancer cells. That is expected to change as projects like TCGA, TARGET, and CGCI yield a comprehensive catalog that researchers can use to find new targets for medicines and discover clues to improve patient outcomes. But there is an urgent need for an efficient and user-friendly portal to give researchers access to the data. The NCI genome projects are producing staggering amounts of data.

“The scale of this is far beyond anything faced in medical research before,” Haussler said. “Each genome file, the DNA record from a tumor or normal tissue, is 300 billion bytes. And for every case there are two of these files, the cancer genome and the normal genome. Add to this RNA sequence data, and the prospect of deeper sequencing in the future, and we must plan for up to a terabyte (1,000 billion bytes) for each case.”

TCGA currently generates about 10 terabytes of data each month. For comparison, the Hubble Space Telescope amassed about 45 terabytes of data in its first 20 years of operation. TCGA’s output will increase tenfold or more over the next two years. Over the next four years, if the project produces a terabyte of DNA and RNA data from each of more than 10,000 patients, it will have produced 10 petabytes of data (a petabyte is 1,000 terabytes). And TCGA is just the beginning of the data deluge, Haussler said, noting that 10,000 cases is a small fraction of the 1.5 million new cancer cases diagnosed every year in the United States alone.

New data compression schemes are expected to reduce the total storage space needed, so the CGHub repository is designed initially to hold 5 petabytes and to allow further growth as needed. That is still a massive amount of data, and CGHub will need to accommodate transfers of extremely large data files.

Managed by the UCSC team, the CGHub computer system is located at the San Diego Supercomputer Center. It is connected by high-performance national research networks to major centers nationwide that are participating in these projects, including UCSC. Haussler’s team designed and oversees the storage and computing infrastructure for the repository, which has an automated query and download interface for large-scale, high-speed use. It will eventually also include an interactive web-based interface to allow researchers to browse and query the system and download custom datasets.

It may take years for cancer genomics research to bring about major changes in cancer care. The first step, and the focus of the NCI cancer genomics programs, is to determine which genomic changes are involved in each type of cancer and to understand the molecular and clinical effects of those changes. Then biomedical researchers must identify or develop treatments to block those effects.

“Right now, cancer research needs something on a very large scale, like the Large Hadron Collider in physics,” Haussler said. “Instead of bringing subatomic particles together in high-energy collisions and computing their behavior, we’re bringing cancer genomes together in a common database and computing the disease drivers.”

The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma

Professor David Tuveson and his colleagues turned to mice carrying a faulty version of a gene called KRAS, which puts them at high risk of developing pancreatic cancer. Previous research has shown that this accurately reflects what’s going on in humans, providing a good lab model for studying the disease.

To hunt for new genes involved in pancreatic cancer, the researchers used a “jumping gene” (transposon), known as Sleeping Beauty, which can hop around within an organism’s DNA. When Sleeping Beauty lands within a gene or a region controlling a gene’s activity, it stops it from working properly.

Under normal circumstances, mice with faulty KRAS genes develop pancreatic cancer relatively late in their lives. So the researchers looked for animals that developed the disease very quickly, where Sleeping Beauty must have ‘jumped’ into a gene that normally helps to protect against pancreatic cancer.

As expected, their experiment revealed a number of genes that have already been implicated in pancreatic cancer in humans, proving that their approach was working. But in over a hundred tumours from mice with ‘early’ cancer, they found that Sleeping Beauty had hopped into a gene called USP9X, which hasn’t previously been pinpointed as playing a role in pancreatic cancer.

The researchers found that switching off USP9X in mouse pancreatic cells (using a technique called RNAi) made them grow out of control and stopped them from dying when they should – key characteristics of cancer cells.  These experiments strongly suggested that the gene is involved in pancreatic cancer, so why hadn’t previous studies uncovered it?

The answer came when the researchers turned to samples of pancreatic tumours taken from patients.  They found very low levels of USP9X activity in samples from patients whose cancers had spread aggressively, but – surprisingly – didn’t find faults in the actual gene This initially seems a bit strange, but there are additional mechanisms other than being faulty that can switch a gene on or off.

The researchers had an inkling of what might be going on, and so turned next to pancreatic cancer cells growing in the lab. These also had low levels of USP9X activity. But the scientists treated them with two particular drugs – azacytidine and trichostatin A. These drugs are special because they affect the molecular ‘switches’ (known as epigenetic marks) on DNA that tell a cell whether a gene is active or not. As they suspected, they found that the drugs slowed the growth of the cancer cells.

This confirmed that, in the case of USP9X, the gene is active in healthy pancreas cells, helping to protect them against becoming cancerous. But if the ‘switches’ are flipped, then USP9X is inactivated and the cells start growing out of control to form a tumor.

This helps to explain why USP9X hadn’t turned up before, as most genetic screen are designed to look for faults in the genes themselves rather than these epigenetic ‘switches’

The discovery suggests that drugs that alter the epigenetic ‘switches’ on genes may be useful for treating patients. A number of these are currently in clinical trials, and azacytidine is already used to treat some types of cancer. So there are good grounds for future trials investigating the effects of such ‘epigenetic modulator’ drugs in pancreatic cancer patients.