Grant: Project Grant

We seek funding to explore the development of novel therapeutics targeted against a novel class of driver mutation that we recently discovered in several types of hard-to-treat cancer. This mutation affects the U1 small nuclear RNA, a core component of the spliceosome. It is only the third cancer driver mutation identified in a non-coding RNA, and is present in several difficult-to-treat cancer types, including adult chronic lymphocytic leukemia and pediatric cerebellar medulloblastoma. Tumours carrying this mutation have widespread alterations in splicing, leading to activation of several known or suspected oncogenic pathways. Unlike mutations that affect protein components of the spliceosome, the patterns of mis-splicing in U1 mutant cells are identical from tumour to tumour, raising the possibility of creating an off-the-shelf immunotherapy targeted against the neo-antigens present in U1 mutant tumours. This project brings together a team with expertise in computational biology, proteogenomics, immunotherapy, and the management of adult leukemia and pediatric brain cancer.