CIC mutation as a molecular mechanism of acquired resistance to combined braf-mek inhibition in extramedullary multiple myeloma with central nervous system involvement
Da Via MC, Solimando AG, Garitano-Trojaola A, Barrio S, Munawar U, Strifler S, Haertle L, Rhodes N, Teufel E, Vogt C, Lapa C, Beilhack A, Rasche L, Einsele H, Kortuem KM (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 25
Pages Range: 112-118
Journal Issue: 2
DOI: 10.1634/theoncologist.2019-0356
Abstract
Combined MEK-BRAF inhibition is a well-established treatment strategy in BRAF-mutated cancer, most prominently in malignant melanoma with durable responses being achieved through this targeted therapy. However, a subset of patients face primary unresponsiveness despite presence of the activating mutation at position V600E, and others acquire resistance under treatment. Underlying resistance mechanisms are largely unknown, and diagnostic tests to predict tumor response to BRAF-MEK inhibitor treatment are unavailable. Multiple myeloma represents the second most common hematologic malignancy, and point mutations in BRAF are detectable in about 10% of patients. Targeted inhibition has been successfully applied, with mixed responses observed in a substantial subset of patients mirroring the widespread spatial heterogeneity in this genomically complex disease. Central nervous system (CNS) involvement is an extremely rare, extramedullary form of multiple myeloma that can be diagnosed in less than 1% of patients. It is considered an ultimate high-risk feature, associated with unfavorable cytogenetics, and, even with intense treatment applied, survival is short, reaching less than 12 months in most cases. Here we not only describe the first patient with an extramedullary CNS relapse responding to targeted dabrafenib and trametinib treatment, we furthermore provide evidence that a point mutation within the capicua transcriptional repressor (CIC) gene mediated the acquired resistance in this patient.
Involved external institutions
Germany (DE)How to cite
APA:
Da Via, M.C., Solimando, A.G., Garitano-Trojaola, A., Barrio, S., Munawar, U., Strifler, S.,... Kortuem, K.M. (2020). CIC mutation as a molecular mechanism of acquired resistance to combined braf-mek inhibition in extramedullary multiple myeloma with central nervous system involvement. Oncologist, 25(2), 112-118. https://doi.org/10.1634/theoncologist.2019-0356
MLA:
Da Via, Matteo Claudio, et al. "CIC mutation as a molecular mechanism of acquired resistance to combined braf-mek inhibition in extramedullary multiple myeloma with central nervous system involvement." Oncologist 25.2 (2020): 112-118.
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