biostudies-literatureZecena HHealth Science Research InstituteNCATS NIH HHSNational Cancer InstituteNCI NIH HHSUniversity of California, Cancer Research Coordinating CommitteeUniversity of California Senate Graduate Research CouncilNational Science Foundation33https://www.ebi.ac.uk/biostudies/studies/S-EPMC5883534biostudies-literatureUnknown12(1)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 vemurafeBMC systems biologySystems biology analysis of mitogen activated protein kinase inhibitor resistance in malignant melanoma.PMC5883534CA154887HSRIR00 CA154887GRFPCRN-17-427258K99 CA154887UL1 TR001414K07 CA160756CA160756GRC-13Liu JPanchal PSanghera AFilipp FVMeyskens FLTeo SYBainiwal ALiu-Smith FZecena HTveit DFarhat AWang ZSingh SJfalseSystems biology analysis of mitogen activated protein kinase inhibitor resistance in malignant melanoma.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 vemurafe2018-01-01T00:00:00Z2018 Apr2025-04-04T19:34:26.039Z2019-03-26T23:52:11ZS-EPMC58835342961503010.1186/s12918-018-0554-1