Clinical characterization and therapeutic targeting of fusion genes in oncology.

Gene fusions represent important oncogenic driver mutations resulting in aberrant cellular signaling. In up to 17% of all solid tumors at least one gene fusion can be identified. Precision therapy targeting fusion gene signaling has demonstrated effective clinical benefit. Advancements in clinically relevant next-generation sequencing and bioinformatic techniques have enabled expansion of therapeutic opportunity to subpopulations of patients with fusion gene expression. Clinically, tyrosine inhibitors have shown efficacy in treating fusion gene expressing cancers. Fusion genes are also clonal mutations, meaning it is a personal cancer target involving all cancer cells of that patient, not just a subpopulation of cancer cells within the cancer mass. Thus, both fusion signal disruption and immune signal targeting are effective therapeutic directions. This review discusses fusion gene targeting, therapeutic resistance, and molecular biomarkers.