In 1994, Steve Jackson was a fresh-faced academic with a big idea, which decades later would create an entirely new class of cancer medicines. He wanted to study the proteins in our cells that help repair DNA and allow them to keep functioning, speculating that this could unlock secrets to new drugs.
But even though Jackson was already a professor at the University of Cambridge, he was struggling to finance his research project. Few funders wanted to put money behind his untested idea, which might ultimately prove to be a dead end.
With the help of grants from Worldwide Cancer Research – a charity based in Scotland – Jackson found that cells use a protein called poly ADP-ribose polymerase (PARP) to repair themselves. Then an even bigger idea occurred to him: inhibiting PARP could represent a new way of killing cancer cells – by stopping them repairing themselves. After establishing a company called Kudos, Jackson ultimately managed to turn his idea into the drug olaparib, the world’s first PARP inhibitor.
Nearly 30 years after he first conceived the idea of studying DNA repair, olaparib is now approved in a number of countries across multiple cancer types including ovarian cancer, breast cancer, pancreatic cancer and prostate cancer. According to current estimates, the drug has been given to more than 75,000 people around the world – and with more than 100 clinical trials in progress, it could be used to treat even more cancers in future.
“It’s an incredible story,” says Dr Lynn Turner, director of research at Worldwide Cancer Research. “It demonstrates the benefit of funding research at that very early stage where the scientist is taking some risks.”
Worldwide Cancer Research continues to fund scientists with ambitious ideas that may one day go on to save lives. Here are five other projects at the forefront of cancer research.
1 Personalised medicine and miniature tumours
Cancer treatment is increasingly moving in the direction of personalised medicine with the help of mini tumours or organoids, grown from a patient’s own cells. These can then be used by researchers to screen novel drugs. One study from the Institute of Cancer Research, in which scientists grew tumour organoids from patients with colon and oesophageal cancer, found that if a drug worked on the organoid, it worked on the patient in 90% of cases too.
Worldwide Cancer Research is currently funding a project in Barcelona where Spanish researchers are using tumour organoids to try to identify new treatments for hepatoblastoma, the most common form of childhood liver cancer.
“A lot of cancer research is done on very artificial systems, but a flask of cultured cancer cells is not truly representative of what goes on in the body,” says Turner. “Organoids are trying to advance that, and I think they will be increasingly used to show if people are going to respond to certain treatments.”
2 Kinder cancer therapies
Chemotherapy is known to affect people both emotionally and physically, with one study finding that nearly 80% of patients experienced nausea and vomiting following treatment.
Researchers are increasingly trying to find therapies utilising the human immune system, which are more tolerable and come with fewer side effects. Over the past 15 years, King’s College London immunologist Dr John Maher has been investigating a type of immunotherapy called CAR T-cell therapy, which has already shown success in blood cancers.
Maher’s work has yielded a unique CAR T-cell therapy that can treat head and neck cancer, without the same toxicity as chemotherapy or radiotherapy. “When you’re trying to make the patient’s own immune system respond better to the cancer, that’s obviously going to be much better than a drug that just targets any fast-replicating cell in the body,” says Turner.
3 Understanding why cancers spread
While we understand a lot about the various risk factors for developing cancer in the first place, relatively little is known about why certain cancers can spread or metastasise to different parts of the body. Being able to pinpoint a tumour at risk of spreading, and cutting off that threat could help greatly extend the life expectancy for many cases in years to come.
One chink in cancer’s armour is the amount of energy its cells require to spread. At the German cancer research centre in Heidelberg, the Deutsche Krebsforschungszentrum, Dr Michaela Frye is researching whether stopping mitochondria – energy generating structures within cells – from providing this fuel to tumours could be a new way of stopping metastasis. In the last four years, evidence has emerged that a group of enzymes she has been studying are important in cancer. She hopes that they will be exploited for new therapies within the next five years.
4 New genetic clues to cancer
Back in 2004, Prof Kevin Hiom at the University of Dundee began studying a rare genetic disease called Fanconi anaemia, which affects one in 160,000 children worldwide and is caused by mutations in a gene called BRIP1.
As well as physical abnormalities such as heart defects and hearing loss, children with this condition are at a higher risk of developing cancers such as leukaemia and lymphoma.
Hiom’s work led to wider research into possible connections between the BRIP1 gene and cancer. People can now be more accurately diagnosed with Fanconi anaemia, and having a correct diagnosis allows the best care and treatment plans to be implemented. We now also know that various BRIP1 mutations are linked to more than 2% of all cancers – approximately 350,000 cases each year. Improving our understanding of this gene could result in new ways of preventing, diagnosing and treating these cancers.
5 Repurposing an Alzheimer’s drug for brain cancer
Brain tumours are the leading cause of cancer death in the under 40s, largely due to the shortcomings of existing therapies. While patients are typically prescribed radiotherapy, tumours tend to rapidly become resistant to the treatment and continue to grow, while many chemotherapy drugs are unable to cross the blood-brain barrier and reach the cancer cells.
Dr Manuel Valiente and colleagues at the Spanish National Cancer Research Center have uncovered why these tumours are resistant to radiotherapy, and have developed a blood test to identify whether a patient will respond to treatment.
They have also been studying a drug called azeliragon, which had been studied more than a decade earlier as a possible Alzheimer’s treatment. While it had proved ineffective in this regard, Valiente knew that it could reach the brain, and studies began to suggest that it was capable of sensitising tumours that had spread to the brain to radiotherapy.
Combining the blood test and azeliragon could help identify which patients will benefit from radiotherapy, and is another step towards personalised treatment.
The researchers are now running a clinical trial with patients diagnosed with glioblastoma, an aggressive form of brain cancer, to see whether the combination of azeliragon and radiotherapy is safe and can prolong a patient’s survival.
“For glioblastoma, it’s currently a 12 to 18-month survival time after diagnosis, even with treatment,” says Turner. “So anything we can do to make the benefits of radiotherapy last for longer is really important. We need even more research into brain cancer because it’s so specific, and drugs developed for other cancers often can’t reach the brain, so the more of these research projects we can run, the better.”
Find out more about the search for new cures being funded by Worldwide Cancer Research and how you can support the charity’s work
