Acquired Resistance to BRAF/MEK Inhibitor Therapy in BRAF-V-600-mutated Squamous Cell Lung Cancer: Concurrent Evolvement of PTEN and MEK1 Mutations

Therapy with BRAF plus MEK-inhibitor is an approved principle of therapy for BRAF V600-mutated non esmall-cell lung cancer (NSCLC). Therefore, knowledge and understanding of acquired resistance against this therapy is important. In contrast to BRAF V600-mutated malignant melanoma, data describing mechanisms of resistance by NSCLCs harboring a BRAF V600 mutation is scarce. MAPK reactivation, resulting in increased ERK signaling, is key to acquisition of resistance (in malignant melanoma) and can be related to several mechanisms (eg, RAS or MEK1/2 mutations or BRAF amplification). Here, we present a case report demonstrating the development of 2 parallel resistance categories, evolvement of PTEN and MEK1 mutation as mechanisms of resistance to BRAF- plus MEK-inhibitor. This mechanism might play a general role by acquiring resistance in BRAF V600-mutated NSCLC. Furthermore, the BRAF V600 mutation was detected in a rebiopsy in the course of the disease, which underlines the importance of rebiopsies and should encourage physicians to consider rebiopsy in case of progressive disease. (C) 2020 Elsevier Inc. All rights reserved.