Below the Belt Award

Immunotherapy helps some people with advanced kidney cancers and works best if there are “targets” on the cancer. These immunotherapy targets come from changes in the DNA of the cancer cells called mutations. In kidney cancer some of the mutations are caused by a scrambling of the DNA message. The resulting ‘nonsense’ messages are the targets for the immunotherapy. Nonsense mutations in other cancers can be caused when the DNA gets stuck together. These stuck‐together mutations are common in skin cancers like melanoma, where they are caused by ultraviolet radiation. Unexpectedly, these stuck‐together mutations were found for the first time ever last year in kidney cancer. It was only found in one lab, and this perplexing result needs to be rechecked. Why stuck‐together mutations should be in kidney cancer is a bit of a mystery, but notwithstanding, these stuck‐together mutations might cause the ‘nonsense’ targets, they might be why some people with kidney cancer are helped by immunotherapy. ANZUP has been grateful to deliver the UNISON and KEYPAD clinical trials of immunotherapy in people with kidney cancer. Some people on these clinical trials were helped, others unfortunately not. Most people on these trials kindly donated a sample of their cancer for later research projects. We propose to test the cancer samples from the people in the UNISON and KEYPAD clinical trials, to double‐check that the stuck‐together mutations are indeed seen in kidney cancer, and to see if having more or less of the stucktogether mutations predicts who might benefit from immunotherapy or not. In future clinical trials it might help people decide whether to take one immunotherapy treatment or a combination of treatments. And understanding if stuck‐together mutations are truly in kidney cancer will help us learn how kidney cancer forms, and even how it might be prevented.