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UCLA"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJNA665977"],"scientific_name":["Homo sapiens"],"long_description":["Disruption of the MAPK pathway in cancer by kinase inhibition often fails due to pathway reactivation, causing clinical relapse. Among MAPK inhibitors, type I RAF inhibitors are only active against specific BRAF mutants MEK inhibitor monotherapy is associated with limited clinical benefits but may serve as a foundation for combinatorial therapy. Here, we show that type II RAF plus allosteric MEK inhibitors durably blunt the development of acquired MEK inhibitor resistance among cancers with KRAS, NRAS, NF1, BRAFnon-V600 and BRAFV600 mutations, when compared to a combination of type II RAF plus ERK inhibitors. Type II RAF and MEK (versus ERK) inhibitors also display superior capacity to sequester MEK in RAF complexes and uncouple MEK and ERK interaction in acquired resistant tumor subpopulations. Systemically and intratumorally, type II RAF plus MEK inhibitors expand memory and activated/exhausted CD8+ T-cells. Whereas trametinib alone temporally reduces dominant intra-tumoral T-cell clones, type II RAF inhibitor co-treatment reverses this effect and promotes T-cell clonotypic expansion and convergence. Importantly, durably control of tumors by this combination requires CD8+ T-cells. Thus, the prolonged anti-tumor efficacy of type II RAF plus MEK inhibitors reveals exquisite MAPK addiction in common lethal cancer histologies, and the mechanisms include unexpected allosteric perturbation of the MAPK pathway and engagement of anti-tumor CD8+ T-cell immunity. Overall design: This dataset contains the RNA-seq of human melanoma PDXs and cell lines sensitive/resistant to the MEK inhibitor"],"tag":["xref:PubMed:33318037"],"repository":["ENA"],"description_synonyms":["Kinase Kinases, DmErk, extracellular signal-regulated kinase activity, pp44mapk, DSORT, dsor1, MAP-ERK Kinase, Tyro5, Mpk2, D-MEK/Dsor, p42mapk, MEK1/2, T-Lymphocyte, Tumor, PRKMK7, SR2-1, LeMPK3, T Lymphocyte, p44mpk, Alleviating interaction, Dp38, Su(Raf)34B, mitogen-activated protein kinase activity, Kinase, SAPK2, mpk1, SEM, Sem, immature T cell, MAP-k, Immune Processes, Immune Responses, Erk/Map kinase, MAPK-ERK Kinases, pp42, T-Cells, EK5, DERK-A, Dsor2, T, E(sina)7, DSor1, DSOR1, sem, Rl, retention, Map Kinase, Map Kinase Kinase, T Cells, MP kinase activity, DERK, Immune, malignant neoplasm, MBP kinase II activity, Malignancies, dERK, dSor1, Thymus Dependent Lymphocytes, Tumors, ERK-A, MAP kinase 2 activity, dpERK, dpErk, SAPKK4, sor/MEK1, Process, D-sor-1, Mapk, ERK-2, DSor, Erk1, ERK1, ERK2, mapk1a, Erk2, DmMAPK, PMK-2, dp-ERK, PMK-1, not genetically inherited, DRODSOR1, PMK-3, Benign, p41mapk, T-Cell, mapk1b, MapK, MAPK, MAP Kinase Kinases, pMAPK, pMapK, DMEK-1, Mitogen Activated Protein Kinase Kinase, erk2, dSor, mapk, EK1-1, ERKa, T-cell, DmERKA, MAP ERK Kinase, rl/MAPK, BcDNA:RE08694, l(2R)EMS45-39, CAPB, Thymus-Dependent, DmelCG12559, Benign Neoplasms, p38, l(2)41Ac, T-lymphocyte, Thymus-Dependent Lymphocyte, Malignant Neoplasms, C78273, DpErk, DpERK, dMEK, ErkA, ERKA, CT34260, T cell, dpERk, MAPK-ERK, p41, p40, Cells, SAPK, Dsor, T Cell, other neoplasm, MAPK Kinase, pERK, MAPK Kinases, 9030612K14Rik, MEKs, MAPKK7, Thymus-Dependent Lymphocytes, GroupII, MAPK-ERK Kinase, Neoplasms, Benign Neoplasm, 12559, RNA-seq., Malignant, D-mek, EK2-1, Hek5, AA407128, resistance, Dmek, Prkm1, Whole Transcriptome Shotgun Sequencing, p42-MAPK, JNKK2, CG15793, MAP, Map, ERK, Erk, PRKM1, PRKM2, MAPK ERK Kinase, MAPKKs, Malignancy, MKK7, xp42, PCBC, inhibiteur, MEK 7, D-sor, suppressive genetic interaction (sensu inequality), p42 mitogen-activated protein kinase activity, CG18732, ATP:protein phosphotransferase (MAPKK-activated) activity, erk, Neoplasias, Immune Response, inhibidor, Kinase Kinase, mature T cell, rll, DmERK-A, STK26, SOR, Sor, p38-2, D-Mek, D-MEK, Immune Process, T Lymphocytes, myelin basic protein kinase activity, Lymphocyte, Cancer, inhibitors, ert1, DRT, Malignant Neoplasm, Mitogen-Activated Protein Kinase Kinase, MAP-ERK, prkm2, stress-activated kinase activity, prkm1, CT39192, MAP-2 kinase activity, inhibitor, sor, Cell, MK, MEK/Dsor1, p38delta, MT, MAPK ERK Kinases, stress-activated protein kinase activity, mapk2, mapk1, Neoplasm, MBP kinase I activity, MEK, Mek, MAP Kinase, T lymphocyte, D-SOR, D-Sor, Xp42, DmelCG15793, primary cancer, MAPKK, CG12559, Mitogen Activated Protein Kinase Kinases, storage, Kinases, mitogen activated kinase activity, P42MAPK, Su(Raf)2B, dpERK1, mek, SAPKK-4, Lymphocytes, EY2-2, Cancers, MAPK2, malignant tumor, AU018647, D-ERK, dpMAPK, ERT1, EPHT3, Response, sequestering, Neoplasia, SAP kinase activity, MAP kinase 1 activity"],"name_synonyms":["Kinase Kinases, DmErk, extracellular signal-regulated kinase activity, pp44mapk, DSORT, dsor1, MAP-ERK Kinase, Tyro5, Mpk2, D-MEK/Dsor, p42mapk, MEK1/2, T-Lymphocyte, Tumor, PRKMK7, SR2-1, LeMPK3, T Lymphocyte, p44mpk, Alleviating interaction, Dp38, Su(Raf)34B, mitogen-activated protein kinase activity, Kinase, SAPK2, mpk1, SEM, Sem, immature T cell, MAP-k, Immune Processes, Immune Responses, Erk/Map kinase, MAPK-ERK Kinases, pp42, T-Cells, EK5, DERK-A, Dsor2, T, E(sina)7, DSor1, DSOR1, sem, Rl, retention, Map Kinase, Map Kinase Kinase, T Cells, MP kinase activity, DERK, Immune, malignant neoplasm, MBP kinase II activity, Malignancies, dERK, dSor1, Thymus Dependent Lymphocytes, Tumors, ERK-A, MAP kinase 2 activity, dpERK, dpErk, SAPKK4, sor/MEK1, Process, D-sor-1, Mapk, ERK-2, DSor, Erk1, ERK1, ERK2, mapk1a, Erk2, DmMAPK, PMK-2, dp-ERK, PMK-1, not genetically inherited, DRODSOR1, PMK-3, Benign, p41mapk, T-Cell, mapk1b, MapK, MAPK, MAP Kinase Kinases, pMAPK, pMapK, DMEK-1, Mitogen Activated Protein Kinase Kinase, erk2, dSor, mapk, EK1-1, ERKa, T-cell, DmERKA, MAP ERK Kinase, rl/MAPK, BcDNA:RE08694, l(2R)EMS45-39, CAPB, Thymus-Dependent, DmelCG12559, Benign Neoplasms, p38, l(2)41Ac, T-lymphocyte, Thymus-Dependent Lymphocyte, Malignant Neoplasms, C78273, DpErk, DpERK, dMEK, ErkA, ERKA, CT34260, T cell, dpERk, MAPK-ERK, p41, p40, Cells, SAPK, Dsor, T Cell, other neoplasm, MAPK Kinase, pERK, MAPK Kinases, 9030612K14Rik, MEKs, MAPKK7, Thymus-Dependent Lymphocytes, GroupII, MAPK-ERK Kinase, Neoplasms, Benign Neoplasm, 12559, RNA-seq., Malignant, D-mek, EK2-1, Hek5, AA407128, resistance, Dmek, Prkm1, Whole Transcriptome Shotgun Sequencing, p42-MAPK, JNKK2, CG15793, MAP, Map, ERK, Erk, PRKM1, PRKM2, MAPK ERK Kinase, MAPKKs, Malignancy, MKK7, xp42, PCBC, inhibiteur, MEK 7, D-sor, suppressive genetic interaction (sensu inequality), p42 mitogen-activated protein kinase activity, CG18732, ATP:protein phosphotransferase (MAPKK-activated) activity, erk, Neoplasias, Immune Response, inhibidor, Kinase Kinase, mature T cell, rll, DmERK-A, STK26, SOR, Sor, p38-2, D-Mek, D-MEK, Immune Process, T Lymphocytes, myelin basic protein kinase activity, Lymphocyte, Cancer, inhibitors, ert1, DRT, Malignant Neoplasm, Mitogen-Activated Protein Kinase Kinase, MAP-ERK, prkm2, stress-activated kinase activity, prkm1, CT39192, MAP-2 kinase activity, inhibitor, sor, Cell, MK, MEK/Dsor1, p38delta, MT, MAPK ERK Kinases, stress-activated protein kinase activity, mapk2, mapk1, Neoplasm, MBP kinase I activity, MEK, Mek, MAP Kinase, T lymphocyte, D-SOR, D-Sor, Xp42, DmelCG15793, primary cancer, MAPKK, CG12559, Mitogen Activated Protein Kinase Kinases, storage, Kinases, mitogen activated kinase activity, P42MAPK, Su(Raf)2B, dpERK1, mek, SAPKK-4, Lymphocytes, EY2-2, Cancers, MAPK2, malignant tumor, AU018647, D-ERK, dpMAPK, ERT1, EPHT3, Response, sequestering, Neoplasia, SAP kinase activity, MAP kinase 1 activity"],"additional_accession":[]},"is_claimable":false,"name":"Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Anti-Tumor T-cell Immunity [RNA-seq]","description":"Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Anti-Tumor T-cell Immunity [RNA-seq]","dates":{"last_updated":"2025-09-24","first_public":"2021-06-07"},"accession":"PRJNA665977","cross_references":{"GEO":["GSE158607"],"taxon":["9606"],"PubMed":["33318037"]}}