Result
| Gene | Variant | Type | Tumor | Drug | Drug level | Reference | More | ||||||||||||||||||||||||||||||||||||||
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| ABL1 | ABL1-BCR | FUS | Acute Myeloid Leukemia | Imatinib | I | 1 | |||||||||||||||||||||||||||||||||||||||
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Evidence region
CIVIC Patient Criteria- NoteTreatment of Philadelphia chromosome positive leukemias with imatinib results in high rates of complete remission in patients with CML. Gene name
Full name
ABL proto-oncogene 1, non-receptor tyrosine kinase Gene typeprotein-coding FunctionThis gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014] Drug name
Imatinib DrugBank ID SynonymsImatinib Imatinib Teva Imatinib is a small molecule kinase inhibitor used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec (USA) or Glivec (Europe/Australia) as its mesylate salt, imatinib mesilate (INN). It is occasionally referred to as CGP57148B or STI571 (especially in older publications). It is used in treating chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies. It is the first member of a new class of agents that act by inhibiting particular tyrosine kinase enzymes, instead of non-specifically inhibiting rapidly dividing cells. Target gene
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| ALK | A348D | MUT | Acute Myeloid Leukemia | Crizotinib | V | 1 | |||||||||||||||||||||||||||||||||||||||
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Evidence region
CGI Patient Criteria- NoteThe ALK A348D and F856S extracellular mutations were highly sensitive to the approved ALK inhibitor, crizotinib, and a variety of other ALK inhibitors in clinical development. As we move towards individualized cancer therapy based on mutational profiles of patient tumors, ALK point mutations, although present in a small percentage of samples, represent an exciting therapeutic target. Characterization of additional ALK mutations and demonstration of clinical efficacy will be required to fully implement ALK directed therapy for leukemia patients. Gene name
Full name
ALK receptor tyrosine kinase Gene typeprotein-coding FunctionThis gene encodes a receptor tyrosine kinase, which belongs to the insulin receptor superfamily. This protein comprises an extracellular domain, an hydrophobic stretch corresponding to a single pass transmembrane region, and an intracellular kinase domain. It plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. This gene has been found to be rearranged, mutated, or amplified in a series of tumours including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. The chromosomal rearrangements are the most common genetic alterations in this gene, which result in creation of multiple fusion genes in tumourigenesis, including ALK (chromosome 2)/EML4 (chromosome 2), ALK/RANBP2 (chromosome 2), ALK/ATIC (chromosome 2), ALK/TFG (chromosome 3), ALK/NPM1 (chromosome 5), ALK/SQSTM1 (chromosome 5), ALK/KIF5B (chromosome 10), ALK/CLTC (chromosome 17), ALK/TPM4 (chromosome 19), and ALK/MSN (chromosome X).[provided by RefSeq, Jan 2011] Drug name
Crizotinib DrugBank ID Synonyms(R)-crizotinib Xalkori DescriptionCrizotinib an inhibitor of receptor tyrosine kinase for the treatment of non-small cell lung cancer (NSCLC). Verification of the presence of ALK fusion gene is done by Abbott Molecular's Vysis ALK Break Apart FISH Probe Kit. This verification is used to select for patients suitable for treatment. FDA approved in August 26, 2011. Target gene
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| ALK | F856S | MUT | Acute Myeloid Leukemia | Crizotinib | V | 1 | |||||||||||||||||||||||||||||||||||||||
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Evidence region
CGI Patient Criteria- NoteThe ALK A348D and F856S extracellular mutations were highly sensitive to the approved ALK inhibitor, crizotinib, and a variety of other ALK inhibitors in clinical development. As we move towards individualized cancer therapy based on mutational profiles of patient tumors, ALK point mutations, although present in a small percentage of samples, represent an exciting therapeutic target. Characterization of additional ALK mutations and demonstration of clinical efficacy will be required to fully implement ALK directed therapy for leukemia patients. Gene name
Full name
ALK receptor tyrosine kinase Gene typeprotein-coding FunctionThis gene encodes a receptor tyrosine kinase, which belongs to the insulin receptor superfamily. This protein comprises an extracellular domain, an hydrophobic stretch corresponding to a single pass transmembrane region, and an intracellular kinase domain. It plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. This gene has been found to be rearranged, mutated, or amplified in a series of tumours including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. The chromosomal rearrangements are the most common genetic alterations in this gene, which result in creation of multiple fusion genes in tumourigenesis, including ALK (chromosome 2)/EML4 (chromosome 2), ALK/RANBP2 (chromosome 2), ALK/ATIC (chromosome 2), ALK/TFG (chromosome 3), ALK/NPM1 (chromosome 5), ALK/SQSTM1 (chromosome 5), ALK/KIF5B (chromosome 10), ALK/CLTC (chromosome 17), ALK/TPM4 (chromosome 19), and ALK/MSN (chromosome X).[provided by RefSeq, Jan 2011] Drug name
Crizotinib DrugBank ID Synonyms(R)-crizotinib Xalkori DescriptionCrizotinib an inhibitor of receptor tyrosine kinase for the treatment of non-small cell lung cancer (NSCLC). Verification of the presence of ALK fusion gene is done by Abbott Molecular's Vysis ALK Break Apart FISH Probe Kit. This verification is used to select for patients suitable for treatment. FDA approved in August 26, 2011. Target gene
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| CEBPA | Oncogenic Mutations | MUT | Acute Myeloid Leukemia | Tretinoin | II | 1 | |||||||||||||||||||||||||||||||||||||||
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Evidence region
CIVIC Patient Criteria- NoteIn a randomized trial of previously untreated younger (<60) patients with acute myeloid leukemia (excluding acute promyelocytic leukemia) and high-risk myelodysplastic syndrome CEBPA mutation status had no significant impact on patient response to ATRA (N=20) compared to randomized control (N=15). Gene name
Full name
CCAAT enhancer binding protein alpha Gene typeprotein-coding FunctionThis intronless gene encodes a transcription factor that contains a basic leucine zipper (bZIP) domain and recognizes the CCAAT motif in the promoters of target genes. The encoded protein functions in homodimers and also heterodimers with CCAAT/enhancer-binding proteins beta and gamma. Activity of this protein can modulate the expression of genes involved in cell cycle regulation as well as in body weight homeostasis. Mutation of this gene is associated with acute myeloid leukemia. The use of alternative in-frame non-AUG (GUG) and AUG start codons results in protein isoforms with different lengths. Differential translation initiation is mediated by an out-of-frame, upstream open reading frame which is located between the GUG and the first AUG start codons. [provided by RefSeq, Dec 2013] Drug name
Tretinoin DrugBank ID Synonyms(all-E)-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid Hydroquinone 6% / Tretinoin 0.05% / Triamcinolone 0.025% Tretinoin, also known as all-trans-retinoic acid (ATRA), is a naturally occurring derivative of vitamin A (retinol). Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation and are used to treat acne and photodamaged skin and to manage keratinization disorders such as ichthyosis and keratosis follicularis. Tretinoin also represents the class of anticancer drugs called differentiating agents and is used in the treatment of acute promyelocytic leukemia (APL). Target gene
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| DNMT3A | Oncogenic Mutations | MUT | Acute Myeloid Leukemia | Daunorubicin | I | 1 | |||||||||||||||||||||||||||||||||||||||
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Evidence region
CGI Patient Criteria- NoteWe identified genetic predictors of outcome that improved risk stratification among patients with AML, independently of age, white-cell count, induction dose, and post-remission therapy, and validated the significance of these predictors in an independent cohort. High-dose daunorubicin, as compared with standard-dose daunorubicin, improved the rate of survival among patients with DNMT3A or NPM1 mutations or MLL translocations (P = 0.001) but not among patients with wild-type DNMT3A, NPM1, and MLL (P = 0.67). Gene name
Full name
DNA methyltransferase 3 alpha Gene typeprotein-coding FunctionCpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. [provided by RefSeq, Mar 2016] Drug name
Daunorubicin DrugBank ID Synonyms(+)-Daunomycin Cerubidine A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of leukemia and other neoplasms. Target gene
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| DNMT3A | Oncogenic Mutations | MUT | Acute Myeloid Leukemia | Decitabine | II | 1 | |||||||||||||||||||||||||||||||||||||||
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Evidence region
CIVIC Patient Criteria- NoteAmong 46 AML patients treated with decitabine, the response rate was 75% (6/8) among DNMT3A mutated and 34% (13/38) among DNMT3A wild-type patients (P=.008) Gene name
Full name
DNA methyltransferase 3 alpha Gene typeprotein-coding FunctionCpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. [provided by RefSeq, Mar 2016] Drug name
Decitabine DrugBank ID Synonyms4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-s-triazin-2(1H)-one Dacogen Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic neoplasms with variable underlying etiology and presentation, including neutropenia and thrombocytopenia. Further mutations leading to increased proliferation of cancerous cells can eventually lead to secondary acute myeloid leukemia, which has a poor prognosis.[A215082, A215092] Among treatment options, nucleoside analogues such as decitabine and [azacitidine] integrate into cellular DNA and inhibit the action of DNA methyltransferases, leading to global hypomethylation and related downstream therapeutic benefits.[A2263, A2264, A2265, A215317, L14962] Decitabine was developed by MGI Pharma/SuperGen Inc. and was approved by the FDA for the treatment of MDS on February 5, 2006. It was first marketed under the name Dacogen®.[L14962] It is also available as an oral combination product together with the cytidine deaminase inhibitor [cedazuridine]. Target gene
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| FGFR1 | FGFR1-OP2FGFR1 | FUS | Acute Myeloid Leukemia | Ponatinib | V | 1 | |||||||||||||||||||||||||||||||||||||||
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Evidence region
CIVIC Patient Criteria- NoteIn this preclinial trial, the AML cell line KG1 with FGFR1OP2-FGFR1 mutation was treated with Ponatinib. This drug effectively inhibits both FGFR phosphorylation and viability for KG1 cells at IC50 values 3 nmol/L and 17 nmol/L respectively. Gene name
Full name
fibroblast growth factor receptor 1 Gene typeprotein-coding FunctionThe protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008] Drug name
Ponatinib DrugBank ID SynonymsPonatinib Iclusig DescriptionPonatinib is a novel Bcr-Abl tyrosine kinase inhibitor that is especially effective against the T315I mutation for the treatment of chronic myeloid leukemia. FDA approved on December 14, 2012. Target gene
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| FLT3 | .835. | MUT | Acute Myeloid Leukemia | Gilteritinib | I | 1 | |||||||||||||||||||||||||||||||||||||||
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Evidence region
MyCancerGenome Patient Criteria- Note- Gene name
Full name
fms related receptor tyrosine kinase 3 Gene typeprotein-coding FunctionThis gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. [provided by RefSeq, Jan 2015] Drug name
Gilteritinib DrugBank ID SynonymsGilteritinib BrandXospata DescriptionGilteritinib, also known as ASP2215, is a small molecule part of the FLT3 tyrosine kinase inhibitors that presented a greater selectivity and potency when compared with other agents from this group.[A40036] It is a pyrazinecarboxamide derivative that showed high selectivity to FLT3 preventing the c-Kit -driven myelosuppression observed in other therapies.[A40044] Gilteritinib was developed by Astellas Pharma and FDA approved on November 28, 2018. This drug was approved after being designed as an orphan drug with a fast track and priority review status.[L4830] Target gene
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| FLT3 | .835. | MUT | Acute Myeloid Leukemia | Midostaurin | I | 1 | |||||||||||||||||||||||||||||||||||||||
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Evidence region
MyCancerGenome Patient Criteria- Note- Gene name
Full name
fms related receptor tyrosine kinase 3 Gene typeprotein-coding FunctionThis gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. [provided by RefSeq, Jan 2015] Drug name
Midostaurin DrugBank ID Synonyms4'-N-benzoylstaurosporine Rydapt DescriptionMidostaurin (as Rydapt) is a multitarget kinase inhibitor for the treatment for adult patients with newly diagnosed acute myeloid leukemia (AML) who have a specific genetic mutation called FLT3. It was initially characterized as a potential broad-spectrum antineoplastic agent, with activity toward diverse solid and hematopoietic tumors [A19108]. It was approved on April 28, 2017 and has shown to increase the overall survival rate in patients with AML as an adjunct therapy along with chemotherapeutic agents. Target gene
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| FLT3 | .835. | MUT | Acute Myeloid Leukemia | Gilteritinib | I | 1 | |||||||||||||||||||||||||||||||||||||||
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Evidence region
MyCancerGenome Patient Criteria Note- Gene name
Full name
fms related receptor tyrosine kinase 3 Gene typeprotein-coding FunctionThis gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. [provided by RefSeq, Jan 2015] Drug name
Gilteritinib DrugBank ID SynonymsGilteritinib BrandXospata DescriptionGilteritinib, also known as ASP2215, is a small molecule part of the FLT3 tyrosine kinase inhibitors that presented a greater selectivity and potency when compared with other agents from this group.[A40036] It is a pyrazinecarboxamide derivative that showed high selectivity to FLT3 preventing the c-Kit -driven myelosuppression observed in other therapies.[A40044] Gilteritinib was developed by Astellas Pharma and FDA approved on November 28, 2018. This drug was approved after being designed as an orphan drug with a fast track and priority review status.[L4830] Target gene
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