Breakthrough kidney cancer treatment using genetic mutation could help 2,600 people every year in the UK

A new treatment for kidney cancer could be available within a decade.

Scientists say the combination of radiotherapy and immunotherapy can produce far better results than the sum of its parts and has the potential to affect 2,600 people in the UK each year – almost 100,000 worldwide.

In some cases, patients with early-stage kidney cancer could be cured, while patients with advanced stages of the disease who don’t respond to other treatments could live significantly longer, they say.

Radiation therapy is rarely used to treat kidney cancer because it is much less effective in this specific form of the disease than in other types of cancer. Many cancer patients also do not respond to immunotherapy.

During their research, scientists combined the two treatments for people with a genetic mutation that allows cancer to spread more easily.

Early results suggest that in this patient population, radiation treatment or radiology can significantly improve the effectiveness of immunotherapy, which stimulates people’s immune systems to fight cancer more effectively.

The additional radiation therapy helps by boosting the immune system of these patients – who do not usually respond to immunotherapy – and improving their response to immunotherapy.

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“Our findings could really benefit a large group of people who don’t have many options,” said lead researcher Professor Jessica Downs of the Institute of Cancer Research in London.

“Globally, approximately 120,000 patients with PRBM1 mutations are diagnosed with kidney cancer each year. And less than a quarter of those patients are responding well to immunotherapy,” she said.

dr Navita Somaiah, Research Scientist at the ICR and Clinical Oncologist at the Royal Marsden NHS Foundation Trust, who also worked on the study, said: “This is very exciting preliminary laboratory data that suggests we may be able to combine immunotherapy and radiotherapy more effectively to improve treatment outcomes improve in some high-risk kidney cancer patients. We estimate that there are around 2,600 patients per year in the UK who could potentially benefit.

“Currently, immunotherapy is given as a monotherapy either after surgery or as first-line treatment for advanced kidney cancer. Radiation therapy is mainly reserved for palliation [symptom relief] when surgery is not possible or to treat metastases.”

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The study is published in the journal genes and development. It was jointly funded by Cancer Research UK and the ICR.

PBRM1 explained

The scientists found that when the PBRM1 gene is functioning properly, it is crucial in slowing the spread of cancer by stopping cells with damaged DNA (like that of cancer) from dividing until the damage is repaired is.

They found that mutations in the gene disrupt this process, allowing cells with damaged DNA to multiply more easily, helping the cancer spread.

But by allowing the damaged DNA to multiply, they trigger “inflammatory signals” that are thought to enhance the patient’s anti-cancer immune response, presenting an opportunity to boost the effectiveness of immunotherapy in patients with the mutation they damage the DNA through radiation therapy and trigger the inflammatory signal.

Damaging the DNA in patients without the mutation would not give the patients the same immune system boost because it would not trigger inflammatory signals to the same extent.

Innate immune signaling is the body’s natural response to injury or infection. When cells with DNA damage are allowed to proliferate, they trigger these signaling pathways that alert the immune system to the detected threat and, like in cancer, prompt neighboring cells to ramp up their anti-tumor defenses.

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Radiation therapy is not usually used to treat cancer, which tends to be radioresistant. But rather than killing the cells directly, scientists suggest that the DNA damage caused by radiation therapy could trigger the inflammatory signaling pathway and increase the effects of immunotherapy in patients with PRBM1 mutations, many of whom do not usually respond to treatment.

dr Navita Somaiah, Research Scientist at the ICR and Clinical Oncologist at the Royal Marsden NHS Foundation Trust, said: “This study suggests that we may be able to improve the efficacy of immunotherapy in PBRM1 mutant cancers by altering the DNA Harmful properties of radiation. The combination of radiotherapy and immunotherapy could play a role in preventing the progression of advanced cases, but also in the complete cure of high-risk, early-stage cancer patients.”

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