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US 2014/0349878 A1Published application
Paclitaxel response markers for cancer
AssigneeNational Research Council of Canada
InventorsEdwin Wang, Jie Li, Maureen O'Connor-McCourt, Enrico Purisima
Life of this patent
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Abstract
Cancer marker sets consisting of particular genes differentially expressed in tumours provide improved accuracy of predicting effectiveness of paclitaxel or paclitaxel-like drug treatment against a cancer. These sets are further useful for screening drug candidates for paclitaxel-like cancer treatment activity. The cancer marker sets may be used in a clinical setting to provide information about the likelihood that a cancer patient would or would not respond to paclitaxel or paclitaxel-like drug treatment.
Claims18
A method of determining likelihood that a tumour in a patient would be treatable with paclitaxel or a paclitaxel-like drug, the method comprising:
- (a) obtaining a gene expression list of a sample of the tumour or an extract of the tumour having message RNA therein of the patient;
- (b) determining a gene expression profile of the sample from the gene expression list for genes of a gene marker set;
- and,
- (c) comparing the gene expression profile of the sample to standardized “good” and “bad” profiles of the marker set to determine whether the gene expression profile of the sample predicts that the tumour is treatable or not treatable with paclitaxel or a paclitaxel-like drug, wherein “good” indicates that the tumour is likely treatable with paclitaxel or a paclitaxel-like drug and “bad” indicates that the tumour is not likely treatable with paclitaxel or a paclitaxel-like drug,
- and the gene marker set is Set 1, Set 2, Set 3, Set 4, Set 5, Set 6 or a combination thereof, wherein
- Set 1 consists of:
- EntrezGene
- Gene
- ID
- Full Name of Gene
- HELLS
- 3070
- Helicase, lymphoid-specific
- CDC2
- 983
- Cell division cycle 2, G1 to S and G2 to M
- PLEKHF1
- 79156
- Pleckstrin homology domain containing,
- family F (with FYVE domain) member 1
- IGFBP3
- 3486
- Insulin-like growth factor binding protein 3
- CASP3
- 836
- Caspase 3, apoptosis-related cysteine peptidase
- HRK
- 8739
- Harakiri, BCL2 interacting protein (contains
- only BH3 domain)
- PCSK6
- 5046
- Proprotein convertase subtilisin/kexin type 6
- PLAGL1
- 5325
- Pleiomorphic adenoma gene-like 1
- NME5
- 8382
- Non-metastatic cells 5, protein expressed in
- (nucleoside-diphosphate kinase)
- PROP1
- 5626
- PROP paired-like homeobox 1
- NOD2
- 64127
- Nucleotide-binding oligomerization domain
- containing 2
- CD38
- 952
- CD38 molecule
- ATP7A
- 538
- ATPase, Cu++ transporting, alpha polypeptide
- (Menkes syndrome)
- INDO
- 3620
- Indoleamine-pyrrole 2,3 dioxygenase
- PIM2
- 11040
- Pim-2 oncogene
- ECT2
- 1894
- Epithelial cell transforming sequence 2
- oncogene
- CASP8AP2
- 9994
- CASP8 associated protein 2
- STK17B
- 9262
- Serine/threonine kinase 17b
- PRKDC
- 5591
- Protein kinase, DNA-activated, catalytic
- polypeptide
- CRADD
- 8738
- CASP2 and RIPK1 domain containing adaptor
- with death domain
- BECN1
- 8678
- Beclin 1 (coiled-coil, myosin-like BCL2
- interacting protein)
- CAPN10
- 11132
- Calpain 10
- PRUNE2
- 158471
- Prune homolog 2 (Drosophila)
- SKP2
- 6502
- S-phase kinase-associated protein 2 (p45)
- ANL1
- 25
- V-abl Abelson murine leukemia viral oncogene
- homolog 1
- CLN3
- 1201
- Ceroid-lipofuscinosis, neuronal 3, juvenile
- (Batten, Spielmeyer-Vogt disease)
- CTSB
- 1508
- Cathepsin B
- MUC2
- 4583
- Mucin 2, oligomeric mucus/gel-forming
- NUP62
- 23636
- Nucleoporin 62 kDa
- APOE
- 348
- Apolipoprotein E
- Set 2 consists of:
- EntrezGene
- Gene Name
- ID
- Full Name of Gene
- CENPE
- 1062
- Centromere protein E, 312 kDa
- CENPF
- 1063
- Centromere protein F, 350/400 ka (mitosin)
- AURKB
- 9212
- Aurora kinase B
- TTK
- 7272
- TTK protein kinase
- CDCA8
- 55143
- Cell division cycle associated 8
- SKP1
- 6500
- S-phase kinase-associated protein 1
- CCNA2
- 890
- Cyclin A2
- CAMK2G
- 818
- Calcium/calmodulin-dependent protein kinase
- (CaM kinase) II gamma
- INHBA
- 3624
- Inhibin, beta A
- CDC2
- 983
- Cell division cycle 2, G1 to S and G2 to M
- ERCC6L
- 54821
- Excision repair cross-complementing rodent
- repair deficiency, complementation group 6-like
- BUB1B
- 701
- BUB1 budding uninhibited by benzimidazoles
- 1 homolog beta (yeast)
- NCAPD3
- 23310
- Non-SMC condensin II complex, subunit D3
- CDC25A
- 993
- Cell division cycle 25 homolog A (S. pombe)
- DCC1
- 79075
- Defective in sister chromatid cohesion homolog
- 1 (S. cerevisiae)
- PSMB9
- 5698
- Proteasome (prosome, macropain) subunit,
- beta type, 9 (large multifunctional peptidase 2)
- DLG7
- 9787
- Discs, large homolog 7 (Drosophila)
- CHEK1
- 1111
- CHK1 checkpoint homolog (S. pombe)
- CLASP1
- 23332
- Cytoplasmic linker associated protein 1
- SMC2
- 10592
- Structural maintenance of chromosomes 2
- ZWINT
- 11130
- ZW10 interactor
- SKP2
- 6502
- S-phase kinase-associated protein 2 (p45)
- NCAPG
- 64151
- Non-SMC condensin I complex, subunit G
- DBF4
- 10926
- DBF4 homolog (S. cerevisiae)
- CDC20
- 991
- Cell division cycle 20 homolog (S. cerevisiae)
- STMN1
- 3925
- Stathmin 1/oncoprotein 18
- MDM2
- 4193
- Mdm2, transformed 3T3 cell double minute 2,
- p53 binding protein (mouse)
- TXNL4B
- 54957
- Thioredoxin-like 4B
- ABL1
- 25
- V-abl Abelson murine leukemia viral oncogene
- homolog 1
- NUMA1
- 4926
- Nuclear mitotic apparatus protein 1
- Set 3 consists of:
- EntrezGene
- Gene Name
- ID
- Full Name of Gene
- CCL2
- 6347
- Chemokine (C—C motif) ligand 2
- TAP1
- 6890
- Transporter 1, ATP-binding cassette, sub-
- family B (MDR/TAP)
- CD163
- 9332
- CD163 molecule
- IFIH1
- 64135
- Interferon induced with helicase C domain 1
- SERPINE1
- 5054
- Serpin peptidase inhibitor, clade E (nexin,
- plasminogen activator inhibitor type 1),
- member 1
- RSAD2
- 91543
- Radical S-adenosyl methionine domain
- containing 2
- DHX58
- 79132
- DEXH (Asp-Glu-X-His) box polypeptide 58
- VWF
- 7450
- Von Willebrand factor
- TNFRSF17
- 608
- Tumor necrosis factor receptor superfamily,
- member 17
- TNFRSF4
- 7293
- Tumor necrosis factor receptor superfamily,
- member 4
- PSG9
- 5678
- Pregnancy specific beta-1-glycoprotein 9
- CCR4
- 1233
- Chemokine (C—C motif) receptor 4
- FXN
- 2395
- Frataxin
- PARP1
- 142
- Poly (ADP-ribose) polymerase family,
- member 1
- C1QB
- 713
- Complement component 1, q subcomponent,
- B chain
- PRKDC
- 5591
- Protein kinase, DNA-activated, catalytic
- polypeptide
- CD38
- 952
- CD38 molecule
- APOE
- 348
- Apolipoprotein E
- FKBP1A
- 2280
- FK506 binding protein 1A, 12 kDa
- IL4
- 3565
- Interleukin 4
- PCSK6
- 5046
- Proprotein convertase subtilisin/kexin type 6
- BECN1
- 8678
- Beclin 1 (coiled-coil, myosin-like BCL2
- interacting protein)
- PSMB9
- 5698
- Proteasome (prosome, macropain) subunit,
- beta type, 9 (large multifunctional peptidase 2)
- GALNT2
- 2590
- UDP-N-acetyl-alpha-D-galactosamine:
- polypeptide N-acetylgalactosaminyltransferase
- 2 (GalNAc-T2)
- KLK13
- 26085
- Kallikrein-related peptidase 13
- LAX1
- 54900
- Lymphocyte transmembrane adaptor 1
- GCH1
- 2643
- GTP cyclohydrolase 1 (dopa-responsive
- dystonia)
- CLN3
- 1201
- Ceroid-lipofuscinosis, neuronal 3, juvenile
- (Batten, Spielmeyer-Vogt disease)
- C2
- 717
- Complement component 2
- PSG1
- 5669
- Pregnancy specific beta-1-glycoprotein 1
- Set 4 consists of:
- EntrezGene
- Gene Name
- ID
- Full Name of Gene
- API5
- 8539
- Apoptosis inhibitor 5
- AGT
- 183
- Angiotensinogen (serpin peptidase inhibitor,
- clade A, member 8)
- SAP30BP
- 29115
- SAP30 binding protein
- BNIP3
- 664
- BCL2/adenovirus E1B 19 kDa interacting
- protein 3
- GLI3
- 2737
- GLI-Kruppel family member GLI3 (Greig
- cephalopolysyndactyly syndrome)
- UNC5B
- 219699
- Unc-5 homolog B (C. elegans)
- PDE1B
- 5153
- Phosphodiesterase 1B, calmodulin-dependent
- MSX1
- 4487
- Msh homeobox 1
- HIP1
- 3092
- Huntingtin interacting protein 1
- PDCD10
- 11235
- Programmed cell death 10
- PPARD
- 5467
- Peroxisome proliferator-activated receptor
- LOC283871
- 283871
- Hypothetical protein LOC283871delta
- RRAGA
- 10670
- Ras-related GTP binding A
- ERBB3
- 2065
- V-erb-b2 erythroblastic leukemia viral
- oncogene homolog 3 (avian)
- IHPK2
- 51447
- Inositol hexaphosphate kinase 2
- EEF1A2
- 1917
- Eukaryotic translation elongation factor 1
- alpha 2
- PERP
- 64065
- PERP, TP53 apoptosis effector
- ATP6AP1
- 537
- ATPase, H+ transporting, lysosomal accessory
- protein 1
- ING4
- 51147
- Inhibitor of growth family, member 4
- NLRP2
- 55655
- NLR family, pyrin domain containing 2
- FXR1
- 8087
- Fragile X mental retardation, autosomal
- homolog 1
- C16orf5
- 29965
- Chromosome 16 open reading frame 5
- BLCAP
- 10904
- Bladder cancer associated protein
- VEGFA
- 7422
- Vascular endothelial growth factor A
- ESR1
- 2099
- Estrogen receptor 1
- TRAF5
- 7188
- TNF receptor-associated factor 5
- FIS1
- 51024
- Fission 1 (mitochondrial outer membrane)
- homolog (S. cerevisiae)
- SFRP1
- 6422
- Secreted frizzled-related protein 1
- COMP
- 1311
- Cartilage oligomeric matrix protein
- CDKN2A
- 1029
- Cyclin-dependent kinase inhibitor 2A
- (melanoma, p16, inhibits CDK4)
- Set 5 consists of:
- EntrezGene
- Gene Name
- ID
- Full Name of Gene
- PERP
- 64065
- PERP, TP53 apoptosis effector
- KAL1
- 3730
- Kallmann syndrome 1 sequence
- EFS
- 10278
- Embryonal Fyn-associated substrate
- CLDN3
- 1365
- Claudin 3
- CD36
- 948
- CD36 molecule (thrombospondin receptor)
- ITGA6
- 3655
- Integrin, alpha 6
- CXCL12
- 6387
- Chemokine (C—X—C motif) ligand 12
- (stromal cell-derived factor 1)
- PCDHB3
- 56132
- Protocadherin beta 3
- RHOB
- 388
- Ras homolog gene family, member B
- ITGB1
- 3688
- Integrin, beta 1 (fibronectin receptor, beta
- polypeptide, antigen CD29 includes MDF2,
- MSK12)
- GMDS
- 2762
- GDP-mannose 4,6-dehydratase
- DLG1
- 1739
- Discs, large homolog 1 (Drosophila)
- COL19A1
- 1310
- Collagen, type XIX, alpha 1
- SIGLEC8
- 27181
- Sialic acid binding Ig-like lectin 8
- PPARD
- 5467
- Peroxisome proliferator-activated receptor
- delta
- IGFALS
- 3483
- Insulin-like growth factor binding protein,
- acid labile subunit
- LAMA4
- 3910
- Laminin, alpha 4
- STAB1
- 23166
- Stabilin 1
- PTPRM
- 5797
- Protein tyrosine phosphatase, receptor type, M
- SPAM1
- 6677
- Sperm adhesion molecule 1 (PH-20
- hyaluronidase, zona pellucida binding)
- AGT
- 183
- Angiotensinogen (serpin peptidase inhibitor,
- clade A, member 8)
- ZYX
- 7791
- Zyxin
- PCDH7
- 5099
- Protocadherin 7
- PCDHGB5
- 56101
- Protocadherin gamma subfamily B, 5
- MADCAM1
- 8174
- Mucosal vascular addressin cell adhesion
- molecule 1
- COMP
- 1311
- Cartilage oligomeric matrix protein
- PVRL2
- 5819
- Poliovirus receptor-related 2 (herpesvirus
- entry mediator B)
- LAMA5
- 3911
- Laminin, alpha 5
- PCDHB17
- 54661
- Protocadherin beta 17 pseudogene
- ITGA8
- 8516
- Integrin, alpha 8
- Set 6 consists of:
- EntrezGene
- Gene Name
- ID
- Full Name of Gene
- PDE1B
- 5153
- Phosphodiesterase 1B, calmodulin-dependent
- ITGA6
- 3655
- Integrin, alpha 6
- CCND1
- 595
- Cyclin D1
- DEK
- 7913
- DEK oncogene (DNA binding)
- MSX1
- 4487
- Msh homeobox 1
- CHAF1B
- 8208
- Chromatin assembly factor 1, subunit B (p60)
- TLK1
- 9874
- Tousled-like kinase 1
- SLC25A36
- 55186
- Solute carrier family 25, member 36
- RPS6KB1
- 6198
- Ribosomal protein S6 kinase, 70 kDa,
- polypeptide 1
- USP1
- 7398
- Ubiquitin specific peptidase 1
- AGT
- 183
- Angiotensinogen (serpin peptidase inhibitor,
- clade A, member 8)
- PRKRA
- 8575
- Protein kinase, interferon-inducible double
- stranded RNA dependent activator
- MTMR15
- 22909
- Myotubularin related protein 15
- CHRNA3
- 1136
- Cholinergic receptor, nicotinic, alpha 3
- C16orf5
- 29965
- Chromosome 16 open reading frame 5
- PPARD
- 5467
- Peroxisome proliferator-activated receptor
- delta
- FGB
- 2244
- Fibrinogen beta chain
- ANXA2P2
- 304
- Annexin A2 pseudogene 2
- HSPB1
- 3315
- Heat shock 27 kDa protein 1
- ANXA2
- 302
- Annexin A2
- ESR1
- 2099
- Estrogen receptor 1
- SMAD2
- 4087
- SMAD family member 2
- STAB1
- 23166
- Stabilin 1
- FANCE
- 2178
- Fanconi anemia, complementation group E
- NFATC4
- 4776
- Nuclear factor of activated T-cells,
- cytoplasmic, calcineurin-dependent 4
- ERBB3
- 2065
- V-erb-b2 erythroblastic leukemia viral
- oncogene homolog 3 (avian)
- ERAP1
- 51752
- Endoplasmic reticulum aminopeptidase 1
- TOR1B
- 27348
- Torsin family 1, member B (torsin B)
- HPS5
- 11234
- Hermansky-Pudlak syndrome 5
- RPA3
- 6119
- Replication protein A3, 14 kDa
629 more elements
Dependencies are inferred from the claim text.