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Systems biology analysis of mitogen activated protein kinase inhibitor resistance in malignant melanoma.


ABSTRACT: BACKGROUND:Kinase inhibition in the mitogen activated protein kinase (MAPK) pathway is a standard therapy for cancer patients with activating BRAF mutations. However, the anti-tumorigenic effect and clinical benefit are only transient, and tumors are prone to treatment resistance and relapse. To elucidate mechanistic insights into drug resistance, we have established an in vitro cellular model of MAPK inhibitor resistance in malignant melanoma. METHODS:The cellular model evolved in response to clinical dosage of the BRAF inhibitor, vemurafenib, PLX4032. We conducted transcriptomic expression profiling using RNA-Seq and RT-qPCR arrays. Pathways of melanogenesis, MAPK signaling, cell cycle, and metabolism were significantly enriched among the set of differentially expressed genes of vemurafe

SUBMITTER: Zecena H 

PROVIDER: S-EPMC5883534 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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