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Cambridge study of kidney cancer identifies that existing drugs could help fight renal cell carcinoma





The most comprehensive study of kidney cancer at single-cell level has found that existing drugs could be useful in treating renal cell carcinoma.

The disease, the seventh most common cancer in the UK, has a high mortality rate and is hard to detect.

Micrograph of renal cell carcinoma
Micrograph of renal cell carcinoma

But researchers from the Wellcome Sanger Institute, the University of Cambridge and Cambridge University Hospitals have identified that immune cells known as macrophages that express the gene IL1B as crucial to tumour development.

They say IL1B macrophages are a promising therapeutic target as this cell type has already been targeted using existing drugs that prevent lung cancer.

The researchers studied more than 270,000 single cells and 100 micro-dissections from 12 patients with kidney tumours using single-cell RNA sequencing and mapped the exact location of specific cells within tissues.

Dr Ruoyan Li, from the Wellcome Sanger Institute, first author of a study published in Cancer Cell, said: “Using both single-cell sequencing and spatial transcriptomics allowed us to discover not only what cell types were present in these renal cell carcinoma tumours, but how the cell types were organised in space. This approach meant we could pinpoint macrophages expressing the IL1B gene at the leading edges of tumours, acting almost like a vanguard for tumour growth.”

Three quarters of cases of this cancer and the majority of deaths are caused by clear cell renal cell carcinoma (ccRCC). The disease has a 50 per cent mortality rate, partly because three in five patients show no symptoms until the cancer is at a late stage.

Many RCC tumours form when both copies of the VHL gene are switched off, while a subset of patients have inherited kidney cancer, including Von Hippel-Lindau (VHL) disease - a genetic condition where one copy of the VHL gene is switched off from birth.

The second copy of VHL is usually switched off due to a common genetic event that often occurs in early life, leading to the formation of innumerable tumours.

Those with VHL disease typically suffer numerous and persistent tumours. Kidney tumours can be monitored and surgically removed before the cancer spreads, but new ones form and there is a limit to how many times patients can have surgery before they lose kidney function.

John Hepworth, 62, a VHL patient with RCC, was diagnosed in 2013 at the age of 53 and is a trustee of the VHL UK/Ireland charity.

He said: “We’ve known for decades that there was something going on in our family history, that there was something wrong. Out of the last five generations directly linked to me, four of my family members have died in their forties, and the fifth died at 56.

“I made it to 53 until the disease presented itself, which is fairly late compared to some people. Since being diagnosed my sister and uncle have had genetic testing. While my wife and I don’t have children, my sister and my uncle do, and thankfully they were both negative. I take a lot of comfort knowing that after all these decades, it stops with me.”

The researchers plan clinical trials.

Dr Thomas Mitchell, a senior author of the study from the Wellcome Sanger Institute and the University of Cambridge, said: “I’m optimistic that targeting IL1B macrophages may provide us with a way to treat renal cell carcinomas without resorting to surgery.

“This will be particularly important for patients with VHL disease because we should be able to prevent tumours forming in the first place by focusing on their genetic roots, rather than waiting for them to grow and removing them. As is the case for all cancers, the earlier we can intervene the better.”



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