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|Therapy Name||Midostaurin + Tofacitinib|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Midostaurin||Rydapt||PKC412|CGP 41251||CSF1R Inhibitor 28 FLT3 Inhibitor 64 KIT Inhibitor 57 PKC alpha Inhibitor 6 PKC beta Inhibitor 6 PKC Inhibitor (Pan) 11 VEGFR2 Inhibitor 37||Rydapt (midostaurin) is a multi-kinase inhibitor with activity against FLT3, KIT, PDGFRB, KDR (VEGFR2) and PKC, with higher selectivity for conventional PKC isoforms, which induces cell cycle arrest and apoptosis (PMID: 12124173, PMID: 23127174, PMID: 15914319). Rydapt (midostaurin) is FDA approved for FLT3-mutant AML in combination with chemotherapy, and is approved for use in aggressive systemic mastocytosis, systemic mastocytosis with associated hematological neoplasm, or mast cell leukemia as a single therapy (FDA.gov).|
|Tofacitinib||Xeljanz||Tasocitinib|CP-690550|CP-690,550||JAK Inhibitor (Pan) - ATP competitive 3||Xeljanz (tofacitinib) is a pan-JAK inhibitor, which decreases downstream signaling and potentially leads to reduced tumor cell growth (PMID: 26300391, PMID: 21106989). Xeljanz (tofacitinib) is FDA approved for rheumatoid arthritis (FDA.gov).|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|FLT3 exon 14 ins JAK2 V617F||hematologic cancer||decreased response||Midostaurin + Tofacitinib||Preclinical - Cell culture||Actionable||In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F demonstrated a decreased response to treatment with the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) compared to cells expressing a FLT3-ITD mutation and activating mutations of JAK1 or JAK3 in culture (PMID: 33149267).||33149267|
|FLT3 exon 14 ins JAK3 V722I||hematologic cancer||sensitive||Midostaurin + Tofacitinib||Preclinical - Cell culture||Actionable||In a preclinical study, the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) inhibited cell growth and downstream signaling of transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267).||33149267|
|Clinical Trial||Phase||Therapies||Title||Recruitment Status||Covered Countries||Other Countries|