Targeting dysregulated splicing factor in cancer: lessons learned from RBM10 deficiency

Abstract RNA splicing dysregulation is considered as a molecular hallmark and important therapeutic target of cancer. While targeting splicing has been intensively pursued for cancer therapy, specific modulators for dysregulated splicing factors are generally lacking. RNA binding motif protein 10 (RBM10) is frequently mutated in multiple cancers, in particular lung adenocarcinoma. Increasing evidence demonstrates that RBM10 deficiency due to loss-of-function mutation or aberrant expression contributes to cancer development, progression and therapy response. Here we summarize the functional consequences and new therapeutic implications of RBM10 deficiency in cancer. Using RBM10 as a representative example, we highlight the main strategies and discuss the considerations of targeting dysregulated splicing factors for cancer therapy. Those strategies alone or in combination with currently approved therapies may hold great promise in cancer treatment.