New vulnerability identified in common kidney cancer could open door to new treatments

Published now in Nature Communications, the study led by James Bertlin, a CRUK-funded MBPhD student, and Professor James Nathan (CITIID) has uncovered a new target in the most common form of kidney cancer which offers a dual therapeutic benefit: selectively killing cancer cells while simultaneously activating the immune system to attack them.

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Each year, over 13,000 people in the UK are diagnosed with kidney cancer, which accounts for 4% of all new cancer cases in the UK. Clear cell renal cell cancer accounts for most kidney cancer diagnoses and is defined by loss of the tumour suppressor gene VHL.

Using genome-wide CRISPR/Cas9 screening, the team from the Department of Medicine at the University of Cambridge and the University of Texas Southwestern Medical Center identified the CBF-β gene as a critical dependency in VHL-deficient kidney cancer. Removing CBF-β caused tumour cell death in both cell culture and animal models, with no equivalent effect in normal cells.

Unexpectedly, the team also found that CBF-β loss triggers a potent immune alarm, activating anti-tumour defence through interferon signalling. This reveals a previously unrecognised link between tumour genetics and immune activation.

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What struck us was that this wasn’t simply a matter of finding a cancer cell’s Achilles heel. Removing CBF-β does two things at once: it kills the tumour cell and sends out an immune distress signal. James Nathan, Professor of Respiratory Medicine and Wellcome Senior Clinical Research Fellow, University of Cambridge