Sequential treatment failures in response to BRAF/MEK and immune checkpoint inhibitors mediated by MAP2K2 and B2M mutations in melanoma.

Sequential treatment failures in response to BRAF/MEK and immune checkpoint inhibitors mediated by MAP2K2 and B2M mutations in melanoma.

Publication date: May 10, 2019

Although the treatment of metastatic melanoma has been significantly improved by both anti-BRAF/MEK and checkpoint immunotherapies, resistance to these treatment modalities remains a substantial clinical problem. Multiple clinical studies are addressing the optimal sequencing of these agents in larger patient cohorts, but successful long-term individualized treatment will likely require the elucidation of resistance mechanisms from post-progression samples. Here, we describe a patient with BRAF-V600E-positive metastatic melanoma who was sequentially treated with BRAF/MEK inhibitors (dabrafenib/trametinib) and checkpoint inhibitor immunotherapy (nivolumab, followed by pembrolizumab). After the emergence of resistance, whole exome sequencing was performed, implicating MAP2K2 and B2M mutations in loss of response to anti-BRAF/MEK and anti-PD1 therapies, respectively.

Richmond, C.S., Vallatharasu, Y., Deviley, J.A., Vos, C.R., Parsons, B.M., and Kenny, P.A. Sequential treatment failures in response to BRAF/MEK and immune checkpoint inhibitors mediated by MAP2K2 and B2M mutations in melanoma. 22606. 2019 Exp Mol Pathol.

Concepts Keywords
B2M Trametinib
BRAF Dabrafenib
Exome Breakthrough therapy
Immunotherapies B-Raf inhibitor
Immunotherapy MEK inhibitor
MEK Melanoma
Melanoma Antineoplastic drugs
Patient Cohorts Chemical compounds
Sequencing Cancer treatments
Clinical medicine
Immunotherapy
Immunotherapies
Melanoma treatment

Semantics

Type Source Name
drug DRUGBANK Dabrafenib
gene UNIPROT SLC35G1
disease MESH Multiple
pathway BSID Melanoma
disease DOID melanoma
gene UNIPROT B2M
disease MESH melanoma
gene UNIPROT MAP2K2
gene UNIPROT MAP2K7
disease MESH treatment failures
gene UNIPROT BRAF
gene UNIPROT PDCD1
gene UNIPROT SNCA
gene UNIPROT SPATA2
drug DRUGBANK Pembrolizumab
drug DRUGBANK Nivolumab
drug DRUGBANK Trametinib

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