CA2882759C - Detection of the ntrk1-mprip gene fusion for cancer diagnosis - Google Patents
Detection of the ntrk1-mprip gene fusion for cancer diagnosis Download PDFInfo
- Publication number
- CA2882759C CA2882759C CA2882759A CA2882759A CA2882759C CA 2882759 C CA2882759 C CA 2882759C CA 2882759 A CA2882759 A CA 2882759A CA 2882759 A CA2882759 A CA 2882759A CA 2882759 C CA2882759 C CA 2882759C
- Authority
- CA
- Canada
- Prior art keywords
- ntrk1
- gene fusion
- mprip
- mprip gene
- level
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 63
- 201000011510 cancer Diseases 0.000 title claims abstract description 45
- 108090000623 proteins and genes Proteins 0.000 title claims description 187
- 230000004927 fusion Effects 0.000 title claims description 186
- 238000001514 detection method Methods 0.000 title claims description 22
- 238000003745 diagnosis Methods 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 76
- 238000003556 assay Methods 0.000 claims abstract description 36
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 31
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 28
- 201000005202 lung cancer Diseases 0.000 claims abstract description 28
- 230000000973 chemotherapeutic effect Effects 0.000 claims abstract description 27
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 22
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 72
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 68
- 229920001184 polypeptide Polymers 0.000 claims description 65
- 102000040430 polynucleotide Human genes 0.000 claims description 52
- 239000002157 polynucleotide Substances 0.000 claims description 52
- 108091033319 polynucleotide Proteins 0.000 claims description 52
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 43
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 43
- 102000004169 proteins and genes Human genes 0.000 claims description 29
- 239000012634 fragment Substances 0.000 claims description 28
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims description 28
- 230000027455 binding Effects 0.000 claims description 27
- 239000003112 inhibitor Substances 0.000 claims description 24
- 230000004044 response Effects 0.000 claims description 23
- 101150111783 NTRK1 gene Proteins 0.000 claims description 21
- 239000002299 complementary DNA Substances 0.000 claims description 16
- 238000003757 reverse transcription PCR Methods 0.000 claims description 16
- 239000002146 L01XE16 - Crizotinib Substances 0.000 claims description 15
- 229960005061 crizotinib Drugs 0.000 claims description 15
- KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical group O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 claims description 15
- 230000007783 downstream signaling Effects 0.000 claims description 14
- 230000002596 correlated effect Effects 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 12
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 11
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 11
- UIARLYUEJFELEN-LROUJFHJSA-N LSM-1231 Chemical compound C12=C3N4C5=CC=CC=C5C3=C3C(=O)NCC3=C2C2=CC=CC=C2N1[C@]1(C)[C@](CO)(O)C[C@H]4O1 UIARLYUEJFELEN-LROUJFHJSA-N 0.000 claims description 10
- 239000003481 heat shock protein 90 inhibitor Substances 0.000 claims description 9
- NYNZQNWKBKUAII-KBXCAEBGSA-N (3s)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 NYNZQNWKBKUAII-KBXCAEBGSA-N 0.000 claims description 8
- 241000282414 Homo sapiens Species 0.000 claims description 8
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 8
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 8
- 229950003970 larotrectinib Drugs 0.000 claims description 8
- 230000035945 sensitivity Effects 0.000 claims description 7
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 6
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 6
- 230000009286 beneficial effect Effects 0.000 claims description 6
- WVXNSAVVKYZVOE-UHFFFAOYSA-N DCC-2036 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(F)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=C4C=CC=NC4=CC=3)=CC=2)=C1 WVXNSAVVKYZVOE-UHFFFAOYSA-N 0.000 claims description 5
- 101150003655 Mprip gene Proteins 0.000 claims description 5
- 238000002509 fluorescent in situ hybridization Methods 0.000 claims description 5
- 239000003446 ligand Substances 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- KCOYQXZDFIIGCY-CZIZESTLSA-N (3e)-4-amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1,3-dihydrobenzimidazol-2-ylidene]quinolin-2-one Chemical compound C1CN(C)CCN1C1=CC=C(N\C(N2)=C/3C(=C4C(F)=CC=CC4=NC\3=O)N)C2=C1 KCOYQXZDFIIGCY-CZIZESTLSA-N 0.000 claims description 3
- 229950005778 dovitinib Drugs 0.000 claims description 3
- PHXJVRSECIGDHY-UHFFFAOYSA-N ponatinib Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2N3N=CC=CC3=NC=2)=C1 PHXJVRSECIGDHY-UHFFFAOYSA-N 0.000 claims description 3
- 229950007043 rebastinib Drugs 0.000 claims description 3
- PIQCTGMSNWUMAF-UHFFFAOYSA-N chembl522892 Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C=3C(NC4=CC=CC(F)=C4C=3N)=O)C2=C1 PIQCTGMSNWUMAF-UHFFFAOYSA-N 0.000 claims description 2
- AYOOGWWGECJQPI-NSHDSACASA-N n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-3-(3-propan-2-yloxy-1h-pyrazol-5-yl)imidazo[4,5-b]pyridin-5-amine Chemical compound N1C(OC(C)C)=CC(N2C3=NC(N[C@@H](C)C=4N=CC(F)=CN=4)=CC=C3N=C2)=N1 AYOOGWWGECJQPI-NSHDSACASA-N 0.000 claims description 2
- 238000012109 statistical procedure Methods 0.000 claims description 2
- 229940126496 utatrectinib Drugs 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims 3
- 229940043355 kinase inhibitor Drugs 0.000 abstract description 12
- 239000003757 phosphotransferase inhibitor Substances 0.000 abstract description 12
- 230000001225 therapeutic effect Effects 0.000 abstract description 6
- 230000008901 benefit Effects 0.000 abstract description 4
- 238000012360 testing method Methods 0.000 abstract description 3
- 238000002512 chemotherapy Methods 0.000 abstract 1
- 238000009104 chemotherapy regimen Methods 0.000 abstract 1
- 239000000523 sample Substances 0.000 description 112
- 239000003550 marker Substances 0.000 description 94
- 210000004027 cell Anatomy 0.000 description 93
- 102100035108 High affinity nerve growth factor receptor Human genes 0.000 description 39
- 101000596894 Homo sapiens High affinity nerve growth factor receptor Proteins 0.000 description 38
- 101001028827 Homo sapiens Myosin phosphatase Rho-interacting protein Proteins 0.000 description 35
- 102100037183 Myosin phosphatase Rho-interacting protein Human genes 0.000 description 35
- 238000009396 hybridization Methods 0.000 description 32
- 108020004414 DNA Proteins 0.000 description 30
- 150000007523 nucleic acids Chemical class 0.000 description 30
- 238000011282 treatment Methods 0.000 description 27
- 238000004458 analytical method Methods 0.000 description 23
- 239000003814 drug Substances 0.000 description 21
- 230000005754 cellular signaling Effects 0.000 description 20
- 229940079593 drug Drugs 0.000 description 20
- 102000039446 nucleic acids Human genes 0.000 description 20
- 108020004707 nucleic acids Proteins 0.000 description 20
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 15
- 238000003119 immunoblot Methods 0.000 description 15
- 108091023037 Aptamer Proteins 0.000 description 13
- 239000000427 antigen Substances 0.000 description 13
- 108091007433 antigens Proteins 0.000 description 13
- 102000036639 antigens Human genes 0.000 description 13
- 208000024191 minimally invasive lung adenocarcinoma Diseases 0.000 description 13
- 238000003752 polymerase chain reaction Methods 0.000 description 12
- 230000008707 rearrangement Effects 0.000 description 12
- 239000013598 vector Substances 0.000 description 12
- 101710168331 ALK tyrosine kinase receptor Proteins 0.000 description 11
- 238000005259 measurement Methods 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 10
- 125000000539 amino acid group Chemical group 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 101000686031 Homo sapiens Proto-oncogene tyrosine-protein kinase ROS Proteins 0.000 description 9
- -1 PU24FC1 Chemical compound 0.000 description 9
- 102100023347 Proto-oncogene tyrosine-protein kinase ROS Human genes 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000002441 reversible effect Effects 0.000 description 9
- 239000002246 antineoplastic agent Substances 0.000 description 8
- 210000000349 chromosome Anatomy 0.000 description 8
- 108020001507 fusion proteins Proteins 0.000 description 8
- 102000037865 fusion proteins Human genes 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 108091000080 Phosphotransferase Proteins 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 7
- 229940127089 cytotoxic agent Drugs 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 238000003018 immunoassay Methods 0.000 description 7
- 239000002773 nucleotide Substances 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- 230000026731 phosphorylation Effects 0.000 description 7
- 238000006366 phosphorylation reaction Methods 0.000 description 7
- 102000020233 phosphotransferase Human genes 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 101710154606 Hemagglutinin Proteins 0.000 description 6
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 6
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 6
- 101710176177 Protein A56 Proteins 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 239000013592 cell lysate Substances 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 239000000185 hemagglutinin Substances 0.000 description 6
- 231100000590 oncogenic Toxicity 0.000 description 6
- 230000002246 oncogenic effect Effects 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- 108010002386 Interleukin-3 Proteins 0.000 description 5
- 108010025020 Nerve Growth Factor Proteins 0.000 description 5
- 102000015336 Nerve Growth Factor Human genes 0.000 description 5
- 230000008236 biological pathway Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 238000003364 immunohistochemistry Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 229940053128 nerve growth factor Drugs 0.000 description 5
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 4
- 238000002123 RNA extraction Methods 0.000 description 4
- 230000000890 antigenic effect Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000006285 cell suspension Substances 0.000 description 4
- 230000002759 chromosomal effect Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229960002584 gefitinib Drugs 0.000 description 4
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 210000004940 nucleus Anatomy 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 241000894007 species Species 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 230000004544 DNA amplification Effects 0.000 description 3
- 241000252212 Danio rerio Species 0.000 description 3
- 108010067770 Endopeptidase K Proteins 0.000 description 3
- 241000287828 Gallus gallus Species 0.000 description 3
- 238000000719 MTS assay Methods 0.000 description 3
- 231100000070 MTS assay Toxicity 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 241000282577 Pan troglodytes Species 0.000 description 3
- 241000009328 Perro Species 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 101150035397 Ros1 gene Proteins 0.000 description 3
- 108020004459 Small interfering RNA Proteins 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 125000003275 alpha amino acid group Chemical group 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 239000000090 biomarker Substances 0.000 description 3
- 230000008711 chromosomal rearrangement Effects 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000007850 fluorescent dye Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 208000005017 glioblastoma Diseases 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000016507 interphase Effects 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 238000013507 mapping Methods 0.000 description 3
- 230000031864 metaphase Effects 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 238000011275 oncology therapy Methods 0.000 description 3
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 3
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 230000005945 translocation Effects 0.000 description 3
- 238000010200 validation analysis Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- SWDZPNJZKUGIIH-QQTULTPQSA-N (5z)-n-ethyl-5-(4-hydroxy-6-oxo-3-propan-2-ylcyclohexa-2,4-dien-1-ylidene)-4-[4-(morpholin-4-ylmethyl)phenyl]-2h-1,2-oxazole-3-carboxamide Chemical compound O1NC(C(=O)NCC)=C(C=2C=CC(CN3CCOCC3)=CC=2)\C1=C1/C=C(C(C)C)C(O)=CC1=O SWDZPNJZKUGIIH-QQTULTPQSA-N 0.000 description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- 244000105975 Antidesma platyphyllum Species 0.000 description 2
- 108010077544 Chromatin Proteins 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- 101150040913 DUT gene Proteins 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102100027100 Echinoderm microtubule-associated protein-like 4 Human genes 0.000 description 2
- 101710203446 Echinoderm microtubule-associated protein-like 4 Proteins 0.000 description 2
- RVAQIUULWULRNW-UHFFFAOYSA-N Ganetespib Chemical compound C1=C(O)C(C(C)C)=CC(C=2N(C(O)=NN=2)C=2C=C3C=CN(C)C3=CC=2)=C1O RVAQIUULWULRNW-UHFFFAOYSA-N 0.000 description 2
- JRZJKWGQFNTSRN-UHFFFAOYSA-N Geldanamycin Natural products C1C(C)CC(OC)C(O)C(C)C=C(C)C(OC(N)=O)C(OC)CCC=C(C)C(=O)NC2=CC(=O)C(OC)=C1C2=O JRZJKWGQFNTSRN-UHFFFAOYSA-N 0.000 description 2
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 239000002118 L01XE12 - Vandetanib Substances 0.000 description 2
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 2
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108010006519 Molecular Chaperones Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 206010033701 Papillary thyroid cancer Diseases 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 241000125945 Protoparvovirus Species 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 2
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 2
- 102000004243 Tubulin Human genes 0.000 description 2
- 108090000704 Tubulin Proteins 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000003491 array Methods 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000002230 centromere Anatomy 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 210000003483 chromatin Anatomy 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 230000006552 constitutive activation Effects 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229950006137 dexfosfoserine Drugs 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- QTQAWLPCGQOSGP-GBTDJJJQSA-N geldanamycin Chemical compound N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(OC)C(=O)C=C1C2=O QTQAWLPCGQOSGP-GBTDJJJQSA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 235000009424 haa Nutrition 0.000 description 2
- MCAHMSDENAOJFZ-BVXDHVRPSA-N herbimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](OC)[C@@H](OC)C[C@H](C)[C@@H](OC)C2=CC(=O)C=C1C2=O MCAHMSDENAOJFZ-BVXDHVRPSA-N 0.000 description 2
- 229930193320 herbimycin Natural products 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000000155 isotopic effect Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229950005069 luminespib Drugs 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000005249 lung adenocarcinoma Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000012775 microarray technology Methods 0.000 description 2
- 238000007899 nucleic acid hybridization Methods 0.000 description 2
- 238000002515 oligonucleotide synthesis Methods 0.000 description 2
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 2
- 210000004910 pleural fluid Anatomy 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 239000012474 protein marker Substances 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- OAKGNIRUXAZDQF-TXHRRWQRSA-N retaspimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(O)C1=CC(O)=C2NCC=C OAKGNIRUXAZDQF-TXHRRWQRSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- CYOHGALHFOKKQC-UHFFFAOYSA-N selumetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1Cl CYOHGALHFOKKQC-UHFFFAOYSA-N 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- AYUNIORJHRXIBJ-TXHRRWQRSA-N tanespimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(NCC=C)C(=O)C=C1C2=O AYUNIORJHRXIBJ-TXHRRWQRSA-N 0.000 description 2
- 229950007866 tanespimycin Drugs 0.000 description 2
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 2
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 108010064884 trkA Receptor Proteins 0.000 description 2
- 102000015533 trkA Receptor Human genes 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 229960000241 vandetanib Drugs 0.000 description 2
- UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- 102100031680 Beta-catenin-interacting protein 1 Human genes 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 206010061764 Chromosomal deletion Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 208000004463 Follicular Adenocarcinoma Diseases 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 102100036675 Golgi-associated PDZ and coiled-coil motif-containing protein Human genes 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 102100030595 HLA class II histocompatibility antigen gamma chain Human genes 0.000 description 1
- 101710114425 Homeobox protein Nkx-2.1 Proteins 0.000 description 1
- 101000993469 Homo sapiens Beta-catenin-interacting protein 1 Proteins 0.000 description 1
- 101001072499 Homo sapiens Golgi-associated PDZ and coiled-coil motif-containing protein Proteins 0.000 description 1
- 101001082627 Homo sapiens HLA class II histocompatibility antigen gamma chain Proteins 0.000 description 1
- 101001050559 Homo sapiens Kinesin-1 heavy chain Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 101150017040 I gene Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 101710203526 Integrase Proteins 0.000 description 1
- 102100023422 Kinesin-1 heavy chain Human genes 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 239000002137 L01XE24 - Ponatinib Substances 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000009018 Medullary thyroid cancer Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101710156256 Myosin phosphatase Rho-interacting protein Proteins 0.000 description 1
- 101100384865 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cot-1 gene Proteins 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 description 1
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 108091008611 Protein Kinase B Proteins 0.000 description 1
- 206010056342 Pulmonary mass Diseases 0.000 description 1
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 208000035199 Tetraploidy Diseases 0.000 description 1
- 101710088547 Thyroid transcription factor 1 Proteins 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 102100031079 Transcription termination factor 1 Human genes 0.000 description 1
- 101710159262 Transcription termination factor 1 Proteins 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 229920006243 acrylic copolymer Polymers 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- IQXIUTMSTALSFW-VJFOLWCZSA-N carboplatin paclitaxel Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1.O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 IQXIUTMSTALSFW-VJFOLWCZSA-N 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000004568 cement Substances 0.000 description 1
- 238000005285 chemical preparation method Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000003200 chromosome mapping Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000013377 clone selection method Methods 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 210000001608 connective tissue cell Anatomy 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 229940048717 crizotinib 250 mg Drugs 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 229940121647 egfr inhibitor Drugs 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 230000005861 gene abnormality Effects 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 235000021384 green leafy vegetables Nutrition 0.000 description 1
- 229940094991 herring sperm dna Drugs 0.000 description 1
- 210000004754 hybrid cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000001948 isotopic labelling Methods 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- 229940124303 multikinase inhibitor Drugs 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000007481 next generation sequencing Methods 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- 238000003499 nucleic acid array Methods 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229940127013 pan-TRK inhibitor Drugs 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001568 phenolic resin Polymers 0.000 description 1
- DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical class OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229960001131 ponatinib Drugs 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000013615 primer Substances 0.000 description 1
- 239000002987 primer (paints) Substances 0.000 description 1
- 238000002331 protein detection Methods 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000163 radioactive labelling Methods 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 238000007480 sanger sequencing Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000012421 spiking Methods 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000013517 stratification Methods 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000011311 validation assay Methods 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
- G01N33/57492—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds localized on the membrane of tumor or cancer cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- G01N2333/91205—Phosphotransferases in general
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Cell Biology (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Hospice & Palliative Care (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261696002P | 2012-08-31 | 2012-08-31 | |
| US61/696,002 | 2012-08-31 | ||
| US201361827514P | 2013-05-24 | 2013-05-24 | |
| US61/827,514 | 2013-05-24 | ||
| PCT/US2013/057495 WO2014036387A2 (en) | 2012-08-31 | 2013-08-30 | Methods for diagnosis and treatment of cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2882759A1 CA2882759A1 (en) | 2014-03-06 |
| CA2882759C true CA2882759C (en) | 2018-11-20 |
Family
ID=50184648
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2882759A Expired - Fee Related CA2882759C (en) | 2012-08-31 | 2013-08-30 | Detection of the ntrk1-mprip gene fusion for cancer diagnosis |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20150218652A1 (enExample) |
| EP (1) | EP2890815B1 (enExample) |
| JP (1) | JP6223451B2 (enExample) |
| CA (1) | CA2882759C (enExample) |
| WO (1) | WO2014036387A2 (enExample) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT2350075E (pt) | 2008-09-22 | 2014-06-09 | Array Biopharma Inc | Compostos imidazo[1,2b]piridazina substituídos como inibidores da trk cinase |
| ME03010B (me) | 2008-10-22 | 2018-10-20 | Array Biopharma Inc | Jedinjenja supstituisanog pirazol0[1,5-]pirimidina као inhibitori trk kinaze |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| PL2918588T3 (pl) | 2010-05-20 | 2017-10-31 | Array Biopharma Inc | Związki makrocykliczne jako inhibitory kinazy TRK |
| WO2013059740A1 (en) | 2011-10-21 | 2013-04-25 | Foundation Medicine, Inc. | Novel alk and ntrk1 fusion molecules and uses thereof |
| EP2914621B1 (en) * | 2012-11-05 | 2023-06-07 | Foundation Medicine, Inc. | Novel ntrk1 fusion molecules and uses thereof |
| EP4223770A3 (en) | 2012-11-05 | 2023-10-18 | Foundation Medicine, Inc. | Novel fusion molecules and uses thereof |
| WO2014113729A2 (en) | 2013-01-18 | 2014-07-24 | Foundation Mecicine, Inc. | Methods of treating cholangiocarcinoma |
| WO2015184443A1 (en) * | 2014-05-30 | 2015-12-03 | The Regents Of The University Of Colorado | Activating ntrk1 gene fusions predictive of kinase inhibitor therapy |
| TWI767858B (zh) | 2014-11-16 | 2022-06-11 | 美商亞雷生物製藥股份有限公司 | (S)-N-(5-((R)-2-(2,5-二氟苯基)-吡咯啶-1-基)-吡唑并[1,5-a]嘧啶-3-基)-3-羥基吡咯啶-1-甲醯胺硫酸氫鹽結晶型 |
| HK1255330A1 (zh) | 2015-08-26 | 2019-08-16 | 缆图药品公司 | 适用於治疗与ntrk相关的病症的化合物和组合物 |
| CA3003153A1 (en) | 2015-10-26 | 2017-05-04 | Loxo Oncology, Inc. | Point mutations in trk inhibitor-resistant cancer and methods relating to the same |
| WO2017087778A1 (en) | 2015-11-19 | 2017-05-26 | Blueprint Medicines Corporation | Compounds and compositions useful for treating disorders related to ntrk |
| DK3439662T3 (da) | 2016-04-04 | 2024-09-02 | Loxo Oncology Inc | Væskeformige formuleringer af (s)-n-(5-((r)-2-(2,5-difluorphenyl)-pyrrolidin-1-yl)-pyrazol[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidin-1-carboxamid |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| EP3458456B1 (en) | 2016-05-18 | 2020-11-25 | Loxo Oncology Inc. | Preparation of (s)-n-(5-((r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| CN111886006B (zh) | 2018-01-31 | 2024-07-09 | 德西费拉制药有限责任公司 | 治疗肥大细胞增多症的组合疗法 |
| AU2019215081B2 (en) | 2018-01-31 | 2024-07-25 | Deciphera Pharmaceuticals, Llc. | Combination therapy for the treatment of gastrointestinal stromal tumors |
| AU2019319109A1 (en) * | 2018-08-07 | 2021-02-25 | In3Bio Ltd. | Methods and compositions for inhibition of EGF/EGFR pathway in cobination with anaplastic lymphoma kinase inhibitors |
| WO2020185812A1 (en) | 2019-03-11 | 2020-09-17 | Teva Pharmaceuticals International Gmbh | Solid state forms of ripretinib |
| CN109988836B (zh) * | 2019-03-18 | 2022-06-07 | 厦门艾德生物技术研究中心有限公司 | 一种检测ntrk融合的fish探针组及其应用 |
| WO2021030405A1 (en) | 2019-08-12 | 2021-02-18 | Deciphera Pharmaceuticals, Llc | Ripretinib for treating gastrointestinal stromal tumors |
| MX2022001863A (es) | 2019-08-12 | 2022-05-30 | Deciphera Pharmaceuticals Llc | Metodos para tratar los tumores del estroma gastrointestinal. |
| FI4084779T3 (fi) | 2019-12-30 | 2024-12-16 | Deciphera Pharmaceuticals Llc | 1-(4-bromi-5-(1-etyyli-7-(metyyliamino)-2-okso-1,2-dihydro-1,6-naftyridin-3-yyli)-2-fluorifenyyli)-3-fenyyliurean koostumuksia |
| CN119970649A (zh) | 2019-12-30 | 2025-05-13 | 德西费拉制药有限责任公司 | 非晶型激酶抑制剂制剂及其使用方法 |
| WO2021138391A1 (en) | 2019-12-30 | 2021-07-08 | Tyra Biosciences, Inc. | Indazole compounds |
| WO2021173679A1 (en) * | 2020-02-28 | 2021-09-02 | Advanced Cell Diagnostics, Inc. | Methods for detecting ntrk gene fusion using rna in situ hybridization |
| US11779572B1 (en) | 2022-09-02 | 2023-10-10 | Deciphera Pharmaceuticals, Llc | Methods of treating gastrointestinal stromal tumors |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7122655B2 (en) * | 2002-11-15 | 2006-10-17 | New England Medical Center Hospital, Inc. | Compositions involving M-RIP, and related methods for screening for anti-hypertensive agents, and uses thereof |
| PL2450437T3 (pl) * | 2006-04-14 | 2017-12-29 | Cell Signaling Technology Inc | Defekty genu i zmutowana kinaza ALK w ludzkich guzach litych |
| EP2082035A4 (en) * | 2006-09-15 | 2014-05-07 | Univ Alberta | AUTOMATED FISH ANALYSIS, CIRCULATION MICROFLUID CHIP AND METHOD FOR IMMOBILIZING CELLS ON A MICROFLUID CHIP |
| CA2725978A1 (en) * | 2008-05-28 | 2009-12-03 | Genomedx Biosciences, Inc. | Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer |
| ES2700098T3 (es) * | 2009-05-15 | 2019-02-14 | Insight Genetics Inc | Métodos relacionados con las fusiones de ALK para diagnosticar el cáncer |
| EP2499486A4 (en) * | 2009-11-13 | 2013-11-27 | Infinity Pharmaceuticals Inc | COMPOSITIONS, KITS AND METHODS OF IDENTIFICATION, ASSESSMENT, PREVENTION AND THERAPY OF CANCER |
| WO2013059740A1 (en) * | 2011-10-21 | 2013-04-25 | Foundation Medicine, Inc. | Novel alk and ntrk1 fusion molecules and uses thereof |
| EP2914621B1 (en) * | 2012-11-05 | 2023-06-07 | Foundation Medicine, Inc. | Novel ntrk1 fusion molecules and uses thereof |
-
2013
- 2013-08-30 WO PCT/US2013/057495 patent/WO2014036387A2/en not_active Ceased
- 2013-08-30 CA CA2882759A patent/CA2882759C/en not_active Expired - Fee Related
- 2013-08-30 JP JP2015530089A patent/JP6223451B2/ja not_active Expired - Fee Related
- 2013-08-30 EP EP13832208.6A patent/EP2890815B1/en not_active Not-in-force
- 2013-08-30 US US14/423,867 patent/US20150218652A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP2890815A4 (en) | 2016-05-11 |
| WO2014036387A2 (en) | 2014-03-06 |
| US20150218652A1 (en) | 2015-08-06 |
| CA2882759A1 (en) | 2014-03-06 |
| WO2014036387A3 (en) | 2014-05-08 |
| EP2890815A2 (en) | 2015-07-08 |
| JP6223451B2 (ja) | 2017-11-01 |
| JP2015528295A (ja) | 2015-09-28 |
| EP2890815B1 (en) | 2019-03-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2882759C (en) | Detection of the ntrk1-mprip gene fusion for cancer diagnosis | |
| US20170114415A1 (en) | Activating ntrk1 gene fusions predictive of kinase inhibitor therapy | |
| Lee et al. | Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma | |
| US9216172B2 (en) | Method for determining effectiveness of cancer treatment by assessing the presence of a KIF5B-RET chimeric gene | |
| US20190389969A1 (en) | Ntrk2 fusions | |
| Moelans et al. | Current technologies for HER2 testing in breast cancer | |
| US20200172981A1 (en) | Raf1 fusions | |
| DK2456889T3 (en) | Markers of endometrial cancer | |
| JP7037836B2 (ja) | タンパク質キナーゼ阻害剤に対する感受性予測用バイオマーカー及びその用途 | |
| JP6534930B2 (ja) | Ｎｔｒｋ３融合体の検出法 | |
| Veeraraghavan et al. | Recurrent and pathological gene fusions in breast cancer: current advances in genomic discovery and clinical implications | |
| CA2957396A1 (en) | Method of determining pik3ca mutational status in a sample | |
| JP2012085556A (ja) | 乳がんの診断方法 | |
| CN106662543B (zh) | 肺癌患者中的非侵入性基因突变检测 | |
| Zhang et al. | Oncogenic Neuregulin 1 gene (NRG1) fusions in cancer: A potential new therapeutic opportunities | |
| JP2006523456A (ja) | 分子細胞遺伝学的方法を用いる癌連鎖遺伝子および治療標的の確認 | |
| JP2009050189A (ja) | 抗癌剤の有効性予測方法 | |
| KR20110106244A (ko) | 간세포암종의 예후 진단용 단일 염기 다형성 | |
| JP7150018B2 (ja) | 新規なｃｉｐ２ａバリアント及びその使用 | |
| JP2012085555A (ja) | 乳がん診断用マーカー | |
| KR20140108910A (ko) | 전이성 뇌종양 진단용 마커 | |
| JP2003528630A (ja) | ヒト遺伝子および発現産物 | |
| KR102788247B1 (ko) | 혈관 육종 진단용 조성물, 키트 및 혈관 육종 진단을 위한 정보제공방법 | |
| US20110269636A1 (en) | Materials and methods for identifying patients at heighten risk for developing her2+ related brain tumors | |
| JP5467256B2 (ja) | 消化器癌検出用血清腫瘍マーカー、消化器癌検出キット、および消化器癌検出方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20150220 |
|
| EEER | Examination request |
Effective date: 20150511 |
|
| MKLA | Lapsed |
Effective date: 20200831 |