The rationale for druggability of CCDC6-tyrosine kinase fusions in lung cancer.

Gene fusions occur in up to 17% of solid tumours. Oncogenic kinases are often involved in such fusions. In lung cancer, almost 30% of patients carrying an activated oncogene show the fusion of a tyrosine kinase to an heterologous gene. Several genes are partner in the fusion with the three kinases ALK, ROS1 and RET in lung. The impaired function of the partner gene, in combination with the activation of the kinase, may alter the cell signaling and promote the cancer cell addiction to the oncogene. Moreover, the gene that is partner in the fusion to the kinase may affect the response to therapeutics and/or promote resistance in the cancer cells. Few genes are recurrent partners in tyrosine kinase fusions in lung cancer, including CCDC6, a recurrent partner in ROS1 and RET fusions, that can be selected as possible target for new strategies of combined therapy including TKi.