Loss of BOP1 confers resistance to BRAF kinase inhibitors in melanoma by activating MAP kinase pathway

Significance Oncogenic mutations in theBRAF gene are found in ∼50% of melanomas and drive melanoma growth. Thus, BRAF kinase inhibitors (BRAFi), such as vemurafenib and dabrafenib, have been developed and used for the treatment of BRAF-mutant metastatic melanoma in clinic. However, the clinical benefits of BRAFi are temporary and short-lived due to the emergence of drug resistance. Although several mechanisms of acquired BRAFi resistance have been identified, the basis for acquired resistance remains unknown in over 40% of melanomas. Identifying a new mechanism of acquired resistance to BRAFi may provide new opportunities to effectively treat BRAF-mutant melanoma. In this study, we have identified Block of Proliferation 1 as a new factor the loss of which results in resistance to BRAFi.