New hope for treating kidney cancer using existing drugs

Credit: Omer Bayraktar and Kenny Roberts

The most comprehensive study of kidney cancer at the single-cell level has uncovered a potential drug target to treat renal cell carcinoma, a cancer with a high mortality rate and difficult to detect. Researchers at the Wellcome Sanger Institute, the University of Cambridge and Cambridge University Hospitals have identified immune cells known as macrophages that express the IL1B gene as crucial to tumor development.

The study, published today in cancer cell, recommends IL1B macrophages as a promising therapeutic target to treat renal cell carcinoma, since this cell type has already been targeted by existing drugs that prevent lung cancer. The next step, which is already being explored, will be clinical trials to prove that IL1B targeting can be used to effectively prevent the formation or progression of RCC.

Renal cell carcinoma (RCC) is the seventh most common cancer in the UK, with three-quarters of cases and most deaths caused by clear cell renal cell carcinoma (ccRCC). The disease has a 50% mortality rate, in part because three out of five patients do not experience symptoms until the cancer is in an advanced stage.

Many RCC tumors form when both copies of the VHL gene are turned off. A subset of patients have inherited kidney cancer, including Von Hippel-Lindau disease (VHL), which is a genetic condition in which one copy of the VHL gene is disabled from birth. The second copy of VHL is usually turned off as a result of a common genetic event that often occurs early in life, leading to the formation of numerous tumors.

In this new study, researchers from the Wellcome Sanger Institute and the University of Cambridge studied more than 270,000 single cells and 100 microdissections from 12 patients with kidney tumors. Samples were taken from different parts of the tumor as well as from normal kidney tissue. These samples were analyzed using single-cell RNA sequencing and spatial transcriptomics to map the exact location of specific cells within tissues.

This analysis highlighted a particular type of immune cell, a macrophage that expresses the IL1B gene, as abundant in the margins of tumors.

“Using single-cell sequencing and spatial transcriptomics allowed us to discover not only which cell types were present in these RCC tumors, but also how the cell types were arranged in space. This approach allowed us to identify macrophages that express the IL1B gene into the tips of tumors, acting almost like a vanguard for tumor growth,” says Dr. Ruoyan Li of the Wellcome Sanger Institute.

The findings will be of particular interest to those with VHL disease, who are likely to suffer from numerous and persistent tumours. Although kidney tumors can be monitored and surgically removed before the cancer spreads to other parts of the body, new ones will form and there is a limit to how many times patients can have surgery before losing kidney function.

“As a result of the research, the outlook for those living with VHL disease has greatly improved in recent years. Even before the VHL gene was identified, the standard of care has always been lifelong surveillance with frequent, painful and expensive surgeries to remove tumors spread within the body,” says Joshua Mann, MPH, director of health for the VHL Alliance.

“We are approaching a new era in the management of VHL disease, with a major paradigm shift that could end these surgeries. A way to treat VHL-related tumors without surgical intervention would be a huge boost for those with the disease. OA VHL Alliance is actively exploring opportunities to strengthen and support these important research efforts.”

Researchers are already planning clinical trials to test whether targeting IL1B macrophages is an effective treatment for RCC. The fact that existing drugs targeting this pathway are proven to be effective in preventing some types of lung cancer offers hope that these trials could provide promising results.

“I’m optimistic that targeting IL1B macrophages may provide us with a way to treat RCCs without resorting to surgery. This will be particularly important for patients with VHL disease because we should be able to prevent tumors from 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 with all cancers, the sooner we can intervene, the better,” says Dr. Thomas Mitchell, Wellcome Sanger Institute and University of Cambridge.

More information:
Ruoyan Li et al, Mapping single-cell transcriptomes in the intratumoral and associated territories of renal cancer, cancer cell (2022). DOI: 10.1016/j.ccell.2022.11.001

Provided by the Wellcome Trust Sanger Institute

Quote: New Hope for Treating Kidney Cancer Using Existing Drugs (2022, Nov 25) retrieved Nov 25, 2022 from

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New hope for treating kidney cancer using existing drugs

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