Progress towards precision functional genomics in cancer

The notion of cancer precision medicine is appealingly simple; given the complete catalog of mutations and cell types present in each patient's tumor, along with sufficient prior knowledge, it should be possible to design a therapeutic strategy that improves outcomes. However, most cancer patients do not yet benefit from cancer precision medicine. A central bottleneck is that most recurrently mutated genes in cancer are found mutated in fewer than 5% of patients and most individual variants are found at exceedingly rare frequencies. As a result, how most of these individual variants function is currently unknown. Improving future clinical predictions requires overcoming this challenge. Here, we describe the current state of the emerging field of “precision functional genomics” which stands to complement existing approaches to improve the interpretation of cancer genomes.