The Institute of Cancer Research

Researchers from the Institute of Cancer Research (ICR) have highlighted the potential benefits of treating bladder cancer with personalised radiotherapy. More than 130,000 patients are treated on the NHS every year with radiotherapy, which works by targeting tumours with X-ray radiation. However, the current use of the treatment usually involves a ‘one size fits all’ approach, in which the dosage is the same in each session. Published in the journal European Urology , the phase 2 RAIDER study was designed to find out whether muscle-invasive bladder cancer can be treated with adaptive radiotherapy, a method that involves changing the volume of radiotherapy depending on the area of the body being targeted. The researchers split 345 patients into one of three groups. Patients in the first group received the same treatment plan in each session, while those in the other two were given one of a number of treatment plans, determined on a case-by-case basis in each session. The researchers found that there were fewer serious long-term side effects six to 18 months after treatment than those reported in previous studies across all three groups, with no evidence that those who received higher dose treatment had any worse side effects compared with those who received standard radiotherapy treatment. Approximately 10,500 new cases of bladder cancer are diagnosed in the UK every year. Healthcare workers face a number of challenges treating the disease and the changing shape and position of the bladder can create complications when delivering targeted radiotherapy. The work was funded by Cancer Research UK, Cancer Australia and the Cancer Society of New Zealand, and also supported by the National Institute of Health and Care Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust. Robert Huddart, professor of urological cancer and honorary consultant clinical oncologist at the Royal Marsden and group leader at the ICR said: “Delivering radiotherapy to the bladder is a challenging process. We are pleased this work into a potential new way of treating bladder cancers has allowed us to deliver effective treatment safely and allowed us to use a high dose which promises to cure more patients, with relatively few long-term side effects. “We look forward to studying this method further to explore its effectiveness versus current treatment options.”

A team of researchers has found that a drug currently used to treat breast cancer could help slow the growth of the rare childhood brain tumour diffuse hemispheric glioma (DHG). Published in the journal Cancer Cell , the research from the Institute of Cancer Research (ICR) and the Dana-Farber Cancer Institute showed that ribociclib could be a potential new drug to target the disease. DHGs are high-grade tumours that typically have a prognosis of 18 to 22 months. The researchers, partly funded by the Brain Tumour Charity and Cancer Research UK, focused on a type of DHG with a specific DNA mutation, known as H3G34-mutant. They discovered that tumour cells disrupt the normal development of neurons and found that targeting the CDK6 protein, which is involved in regulating cell division, could make these cells vulnerable to treatments. Novartis’ ribociclib, a CDK4/6 inhibitor currently sold under the brand name Kisqali, was then used to treat a child with a brain tumour when other treatments had failed. The drug resulted in stable disease for a further 17 months before the tumour started to grow back, which the researchers have described as “remarkable” given that the disease usually progresses within 3.5 months following recurrence. The child is currently undergoing further treatment, more than four years since their initial diagnosis. Chris Jones, professor of childhood brain tumour biology at the ICR, said: “This work shows the importance of understanding how brain tumours develop in order to figure out better ways to treat these patients. “It was a surprise to realise that this type of glioma seemed to arise from developing neurons, but we were able to use this knowledge to find specific vulnerabilities in these cancer cells, which hopefully we can now translate into clinical trials.” The team has outlined that, while ribociclib is not a cure for the disease, the findings are significant and could pave the way for future drug combinations to be explored in clinical trials. Mariella Filbin, co-director of the paediatric neuro-oncology programme at the Dana-Farber Cancer Institute, said: “This is the first time we found functional consequences of aberrant lineage specification in tumour cells – a result that was unexpected at first, but is now setting the stage for new therapeutic avenues in this disease.”

A study led by the Institute of Cancer Research (ICR), the University of Oxford and the University of Manchester has revealed previously unknown genetic causes of colorectal cancer (CRC). Published in Nature , the new research offers an unprecedented view of the genetic landscape of CRC and its response to treatment. CRC is the third most commonly diagnosed cancer globally, with more than 44,000 new cases of the disease diagnosed in the UK every year. Researchers analysed 2,023 bowel cancers from the 100,000 Genomes Project led by Genomics England and NHS England to identify new gene faults that lead to CRC and uncovered new CRC cancer sub-groups with specific genetic characteristics that affect how cancer behaves and responds to treatment. In total, the team identified over 250 key genes that play a crucial role in CRC, as well as four novel common sub-groups based on genetic features, along with several rare CRC sub-groups, which have different patient outcomes and may respond differently to therapy. In addition, the team identified a variety of genetic mutation causes across different regions of the colorectum, highlighting differences in CRC causes between individuals, which could potentially be targeted with existing treatments currently used across other cancers. Commenting on the findings, co-lead researcher and ICR’s professor of cancer genomics, Richard Houlston, said: “This research is a great insight into the biology of CRC, uncovering the clues as to how it develops, grows and responds to treatments… Future studies [can] use these findings to develop tailored treatments for people with CRC based on their genetics.” Dr Henry Wood, lecturer in translational bioinformatics from pathology, University of Leeds’ School of Medicine, added: “We are now in a position to investigate the importance of the microbiome in the development of these cancers and whether we can change it to influence the tumour and improve patient outcomes.” Earlier this year, in June, Bristol Myers Squibb’s KRAS inhibitor Krazati (adagrasib) received accelerated approval from the US Food and Drug Administration alongside cetuximab as a targeted treatment option for adults with locally advanced or metastatic cases of CRC who are carrying the KRASG12C mutation.