Small CERN detector could help radiotherapy precision of head tumours


and the Heidelberg Ion Beam Therapy Center (HIT) at Heidelberg University Hospital. Supplied by Czech company ADVACAM the device, which includes a small Timepix3 pixel detector developed at CERN, enables head and neck tumours to be closely monitored during ion radiotherapy, making them easier to target while helping to limit the treatment’s side effects.


“One of the most advanced methods for treating head and neck tumours involves irradiation with ion beams. This has one unique feature: it can be precisely tailored to the depth inside the human head where the particles should have the maximal effect,” explained Mária Martišíková, the head of the DKFZ team.


Mária Martišíková (left), the project leader from Heidelberg University Hospital and German Cancer Research Center (DKFZ), and DKFZ researcher Laurent Kelleter. (Image Credit: Heidelberg University Hospital / H.Schroeder)


Particle detectors similar to those used by physicists at CERN have now also found a role in a new imaging device now being tested on patients by scientists from the German National Center for Tumor Diseases (NCT), the German Cancer Research Center (DKFZ),


Ion radiation, like other types of irradiation, also has the drawback of affecting healthy tissue areas around the tumour and precise targeting of tumours is particularly challenging in the brain, where damage to the optic nerve or a patient’s memory are possible. X-ray computed tomography (CT) scan images taken before treatment essentially provide a map to target the tumour with ion beams; however further complications can arise during therapy as changes in the skull may evolve that alter the target and until now, physicians have lacked a reliable tool to alert them in case of such a change in the brain.


The new device now offers the potential for improving the navigation of the ion beams inside the head by tracking the secondary particles that are created when ions pass through it.


“Our cameras can register every charged particle of secondary radiation emitted from the patient’s body. It’s like watching balls scattered by a billiard shot. If the balls bounce as expected according to the CT image, we can be sure we are targeting correctly. Otherwise, it’s clear that the ‘map’ no longer applies. Then it is necessary to replan the treatment,” said Lukáš Marek from ADVACAM.


“We hope the new device will show us how often and where the tumour changes occur. It will allow us to reduce the overall irradiated volume of tissue, saving healthy tissue and reducing the side effects of radiotherapy. We will also be able to apply higher doses of radiation to the tumour.” added Martišíková.


“When we started developing pixel detectors for the LHC we had one target in mind – to detect and image each particle interaction and thereby help physicists to unravel the secrets of Nature at high energies. The Timepix detectors were developed by the multidisciplinary Medipix Collaborations whose aims are to take the same technology to new fi elds. Many of those fi elds were completely unforeseen at the beginning and this application is a brilliant example of that,” added Michael Campbell, Spokesperson of the Medipix Collaborations.


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New tools found to halt cancer cell activity


A discovery by the University of Dundee’s Drug Discovery Unit (DDU) and Queen Mary University of London (QMUL) has identifi ed chemical compounds, or tool molecules, that can halt active cancer cells making them vulnerable for elimination by new drug treatments. The tool molecules were used to forces cells from a specifi c type of breast cancer into a pro-senescence state in which they can no longer divide or cause tumour growth; this makes them more sensitive to a second group of tool molecules, called senolytic drugs, which can then eliminate them. The process also has the potential to ‘uncloak’ the cancer cells, making them visible to the body’s immune system, offering further therapeutic opportunities.


The research partners developed this ‘two-punch’ method while looking at basal-like breast cancer (BLBC), which is thought to account for around 8-22% of all cases globally, with the highest BLBC incidence in women from Southern Asian and Black ethnic groups. A team funded by Barts Charity and led by Cleo Bishop, Professor of Senescence at QMUL and Academic Lead for the Phenotypic Screening Facility, uncovered a pathway to force BLBC cells into pro-senescence. The collaboration was then established with Dundee’s DDU which led to the development of tool molecules to promote senescence within the cells.


Drug treatments to deliver the ‘second punch’ of cell elimination are currently being developed elsewhere.


Professor Bishop, said: “At present, the most common treatments for BLBC are surgery and unsophisticated chemotherapy regimens. Consequently, the lack of possible targets for tailored therapies and the aggressive clinical course means that women with BLBC have a particularly poor prognosis. Pro-senescence therapies activate a stable cell cycle arrest halting tumour growth, trigger anti-tumour immune responses and expose cancers to novel treatment regimes called senolyitcs.”


Queen Mary University of London project research team (Credit: QMUL/University of Dundee)


During this research high-content imaging from DDU’s diversity libraries was used to identify the tools. The University of Dundee and pharmaceutical company ValiRx, which focuses on early-stage cancer therapeutics and women’s health, have now signed a fi ve year agreement under which the pro-senescent ‘fi rst punch’ tool molecules are the fi rst to be entered into a 12 month evaluation phase. If successful, this could result in a new company being established as a joint venture with all three parties.


University of Dundee’s Drug Discover Unit research team (Credit: University of Dundee)


Charlotte Green, Head of Business Development at the University of Dundee’s Drug Discovery Unit, said: “The one-two punch approach has gained lots of interest in recent years but currently there is no clinical precedent, by moving the project forward with ValiRx we are leading the way in translating the research to the clinic.”


Dr Suzy Dilly, CEO of ValiRx said: “The strength of the DDU and research facilities at Dundee are very impressive and having reviewed multiple projects from teams there over the past year, we believe that this evaluation agreement will be the fi rst of a series of new projects that can be brought into our pipeline.”


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Combined bacterial defences ward off viruses


Scientists at the University of Southampton have discovered how bacteria can pair up their defence systems, creating a formidable force to fi ght off attack from phage viruses. Because phage viruses, or bacteriophages, can kill harmful bacteria without affecting the good bacteria in our bodies, an understanding of how bacteria respond to attacks of this kind could be crucial in exploring how phage viruses might be harnessed to fi ght infections as an alternative to antibiotics.


Lead author of the study, Dr Franklin Nobrega of the University of Southampton’s School of Biological Sciences said: “Just like how our immune system protects us from harmful germs, bacteria have their own set of defence systems which create a dynamic shield against viral threats. Imagine if your white blood cells, antibodies and killer T-cells all joined forces to fi ght off a virus together. This is exactly what is happening inside bacterial cells.


“We used to think of bacterial defence as a solo act, but it turns out it’s more like a buddy system. A ‘dynamic duo’ of defence systems merge their powers to mount a stronger response than they otherwise would have achieved, potentially saving the cell from destruction.”


Using existing datasets of paired defence systems in the genomes


of some 42,000 bacteria, including E. coli, the researchers looked for those that appeared more frequently then would normally be expected. A selection of these were tested in the lab for enhanced virus immunity and, crucially, ‘synergy - a defence effect in the bacteria which is more powerful than the sum of its parts.


From identifi ed enhanced systems and with further testing, they were able to see for the fi rst time how the partnerships between individual bacterial defences are based on one system using a function from another to improve its activity. Combined, they have a more robust effect than working apart.


Phages are already in use as a last-resort treatment for antibiotic- resistant bacterial infections, a practice known as phage therapy. But by delving into how bacteria defend against these phages, we can supercharge our strategies to make them even more effective at wiping out bacterial cells, offering a glimmer of hope in the battle to keep infections at bay, Dr Nobrega added.


The scientists added that their research will complement efforts already underway to develop phage therapy through public participation initiatives such as The Phage Collection Project and the open science KlebPhaCol project.


Microscope image of bacteria. (Credit: Biomedical Imaging Unit, UHS)


Microscope image of phage virus. (Credit: Biomedical Imaging Unit, UHS.)


The funding for this study was from the Wessex Medical Trust and the National Institutes of Health USA. Findings were published in Cell Host & Microbe.


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