Kinome Profiling to Predict Sensitivity to MAPK Inhibition in Melanoma and to Provide New Insights into Intrinsic and Acquired Mechanism of Resistance.
MAPK pathway
intrinsic and acquired resistance
kinase inhibitors
phosphotyrosine kinase
serine-threonine kinase
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
22 02 2020
22 02 2020
Historique:
received:
20
01
2020
revised:
19
02
2020
accepted:
20
02
2020
entrez:
27
2
2020
pubmed:
27
2
2020
medline:
27
2
2020
Statut:
epublish
Résumé
Mitogen-activated protein kinase (MAPK) inhibition with the combination of BRAF (Rapidly Accelerated Fibrosarcoma) and MEK (Mitogen-activated protein kinase kinase) inhibitors has become the standard of first-line therapy of metastatic melanoma harbouring BRAF V600 mutations. However, about half of the patients present with primary resistance while the remaining develop secondary resistance under prolonged treatment. Thus, there is a need for predictive biomarkers for sensitivity and/or resistance to further refine the patient population likely to benefit from MAPK inhibitors. In this study, we explored a top-down approach using a multiplex kinase assay, first, to discover a kinome signature predicting sensitivity, intrinsic and acquired resistance to MAPK inhibitors in melanoma, and second, to understand the mechanism of resistance using cell lines. Pre-dose tissues from patients (four responders and three non-responders to BRAFi monotherapy) were profiled for phosphotyrosine kinase (PTK) and serine-threonine kinase (STK) activities on a PamChip
Identifiants
pubmed: 32098410
pii: cancers12020512
doi: 10.3390/cancers12020512
pmc: PMC7072684
pii:
doi:
Types de publication
Journal Article
Langues
eng
Commentaires et corrections
Type : ErratumIn
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