Combating acquired resistance to MAPK inhibitors in melanoma by targeting Abl1/2-mediated reactivation of MEK/ERK/MYC signaling

Rakshamani Tripathi; Zulong Liu; Aditi Jain; Anastasia Lyon; Christina Meeks; Dana Richards; Jinpeng Liu; Daheng He; Chi Wang; Marika Nespi; Andrey Rymar; Peng Wang; Melissa Wilson; Rina Plattner

doi:10.1038/s41467-020-19075-3

Nature Communications (Oct 2020)

Combating acquired resistance to MAPK inhibitors in melanoma by targeting Abl1/2-mediated reactivation of MEK/ERK/MYC signaling

Rakshamani Tripathi,
Zulong Liu,
Aditi Jain,
Anastasia Lyon,
Christina Meeks,
Dana Richards,
Jinpeng Liu,
Daheng He,
Chi Wang,
Marika Nespi,
Andrey Rymar,
Peng Wang,
Melissa Wilson,
Rina Plattner

Affiliations

Rakshamani Tripathi: Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine
Zulong Liu: Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine
Aditi Jain: Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine
Anastasia Lyon: Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine
Christina Meeks: Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine
Dana Richards: Department of Pathology, University of Kentucky College of Medicine
Jinpeng Liu: Biostatistics and Bioinformatics Shared Resource Facility, Markey Cancer Center, University of Kentucky College of Medicine
Daheng He: Biostatistics and Bioinformatics Shared Resource Facility, Markey Cancer Center, University of Kentucky College of Medicine
Chi Wang: Biostatistics and Bioinformatics Shared Resource Facility, Markey Cancer Center, University of Kentucky College of Medicine
Marika Nespi: Plexxikon Inc.
Andrey Rymar: Plexxikon Inc.
Peng Wang: Department of Internal Medicine, University of Kentucky, College of Medicine
Melissa Wilson: Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University
Rina Plattner: Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine

DOI: https://doi.org/10.1038/s41467-020-19075-3
Journal volume & issue: Vol. 11, no. 1
pp. 1 – 18

Abstract

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Resistance to BRAF/MEK inhibitors is a major impediment to long-term survival for patients with BRAF-mutant melanomas. Here, the authors show that ABL kinases drive resistance by promoting MEK/ERK reactivation and the FDA-approved ABL kinase inhibitor nilotinib prevents and overcomes resistance.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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