JP2016513456A5 - - Google Patents
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- JP2016513456A5 JP2016513456A5 JP2015562469A JP2015562469A JP2016513456A5 JP 2016513456 A5 JP2016513456 A5 JP 2016513456A5 JP 2015562469 A JP2015562469 A JP 2015562469A JP 2015562469 A JP2015562469 A JP 2015562469A JP 2016513456 A5 JP2016513456 A5 JP 2016513456A5
- Authority
- JP
- Japan
- Prior art keywords
- cancer
- wnt inhibitor
- biomarker
- gene expression
- patient
- 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.)
- Granted
Links
- 102000013814 Wnt Human genes 0.000 claims description 119
- 108050003627 Wnt Proteins 0.000 claims description 119
- 239000003112 inhibitor Substances 0.000 claims description 118
- 206010028980 Neoplasm Diseases 0.000 claims description 85
- 201000011510 cancer Diseases 0.000 claims description 84
- 239000000090 biomarker Substances 0.000 claims description 73
- 230000014509 gene expression Effects 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 44
- 230000009274 differential gene expression Effects 0.000 claims description 34
- 239000008194 pharmaceutical composition Substances 0.000 claims description 26
- 102100023181 Neurogenic locus notch homolog protein 1 Human genes 0.000 claims description 25
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims description 21
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 21
- 230000035945 sensitivity Effects 0.000 claims description 21
- 108700037638 Neurogenic locus notch homolog protein 1 Proteins 0.000 claims description 19
- 239000000523 sample Substances 0.000 claims description 19
- 230000035772 mutation Effects 0.000 claims description 16
- -1 2-methylpyridin-4-yl Chemical group 0.000 claims description 11
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 8
- 239000002299 complementary DNA Substances 0.000 claims description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 8
- 108020004414 DNA Proteins 0.000 claims description 7
- 239000013068 control sample Substances 0.000 claims description 7
- 230000007423 decrease Effects 0.000 claims description 7
- 102000004169 proteins and genes Human genes 0.000 claims description 7
- 102100035683 Axin-2 Human genes 0.000 claims description 6
- 101000972291 Homo sapiens Lymphoid enhancer-binding factor 1 Proteins 0.000 claims description 6
- 101000972806 Homo sapiens Protein naked cuticle homolog 1 Proteins 0.000 claims description 6
- 102100022699 Lymphoid enhancer-binding factor 1 Human genes 0.000 claims description 6
- 102100022560 Protein naked cuticle homolog 1 Human genes 0.000 claims description 6
- 108020004999 messenger RNA Proteins 0.000 claims description 6
- 239000000902 placebo Substances 0.000 claims description 4
- 229940068196 placebo Drugs 0.000 claims description 4
- 101150096411 AXIN2 gene Proteins 0.000 claims description 3
- 230000009946 DNA mutation Effects 0.000 claims description 3
- 230000008836 DNA modification Effects 0.000 claims description 2
- 230000017156 mRNA modification Effects 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims description 2
- 238000012986 modification Methods 0.000 claims description 2
- 230000009145 protein modification Effects 0.000 claims description 2
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 2
- 238000013518 transcription Methods 0.000 claims description 2
- 230000035897 transcription Effects 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims 7
- 230000003247 decreasing effect Effects 0.000 claims 4
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 claims 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 2
- 230000006870 function Effects 0.000 claims 1
- 230000004853 protein function Effects 0.000 claims 1
- 102000001759 Notch1 Receptor Human genes 0.000 description 14
- 108010029755 Notch1 Receptor Proteins 0.000 description 14
- 102000001760 Notch3 Receptor Human genes 0.000 description 13
- 108010029756 Notch3 Receptor Proteins 0.000 description 13
- 108010009392 Cyclin-Dependent Kinase Inhibitor p16 Proteins 0.000 description 10
- 102000009508 Cyclin-Dependent Kinase Inhibitor p16 Human genes 0.000 description 10
- 102100021898 Cyclin-Q Human genes 0.000 description 10
- 102100029974 GTPase HRas Human genes 0.000 description 10
- 101000897449 Homo sapiens Cyclin-Q Proteins 0.000 description 10
- 101000584633 Homo sapiens GTPase HRas Proteins 0.000 description 10
- 101000969828 Homo sapiens Maestro heat-like repeat family member 5 Proteins 0.000 description 10
- 101001121132 Homo sapiens Olfactory receptor 7G3 Proteins 0.000 description 10
- 101000824318 Homo sapiens Protocadherin Fat 1 Proteins 0.000 description 10
- 102100021322 Maestro heat-like repeat family member 5 Human genes 0.000 description 10
- 102100025246 Neurogenic locus notch homolog protein 2 Human genes 0.000 description 10
- 108700037064 Neurogenic locus notch homolog protein 2 Proteins 0.000 description 10
- 102100026603 Olfactory receptor 7G3 Human genes 0.000 description 10
- 102100022095 Protocadherin Fat 1 Human genes 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 102100030091 Dickkopf-related protein 2 Human genes 0.000 description 8
- 101000864647 Homo sapiens Dickkopf-related protein 2 Proteins 0.000 description 8
- 101000946682 Homo sapiens Leucine-rich repeat transmembrane protein CCDC168 Proteins 0.000 description 8
- 101000864786 Homo sapiens Secreted frizzled-related protein 2 Proteins 0.000 description 8
- 101000864793 Homo sapiens Secreted frizzled-related protein 4 Proteins 0.000 description 8
- 101000723599 Homo sapiens Zinc finger protein 527 Proteins 0.000 description 8
- 102100034964 Leucine-rich repeat transmembrane protein CCDC168 Human genes 0.000 description 8
- 102100030054 Secreted frizzled-related protein 2 Human genes 0.000 description 8
- 102100030053 Secreted frizzled-related protein 3 Human genes 0.000 description 8
- 102100030052 Secreted frizzled-related protein 4 Human genes 0.000 description 8
- 108010020277 WD repeat containing planar cell polarity effector Proteins 0.000 description 8
- 102100027804 Zinc finger protein 527 Human genes 0.000 description 8
- 102100023991 E3 ubiquitin-protein ligase DTX3L Human genes 0.000 description 6
- 101000904542 Homo sapiens E3 ubiquitin-protein ligase DTX3L Proteins 0.000 description 6
- 101000781981 Homo sapiens Protein Wnt-11 Proteins 0.000 description 6
- 101000855004 Homo sapiens Protein Wnt-7a Proteins 0.000 description 6
- 102100036567 Protein Wnt-11 Human genes 0.000 description 6
- 102100020729 Protein Wnt-7a Human genes 0.000 description 6
- 101000814371 Homo sapiens Protein Wnt-10a Proteins 0.000 description 5
- 101000954762 Homo sapiens Proto-oncogene Wnt-3 Proteins 0.000 description 5
- 102100039461 Protein Wnt-10a Human genes 0.000 description 5
- 102000052549 Wnt-3 Human genes 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 101000874569 Homo sapiens Axin-2 Proteins 0.000 description 3
- 125000001475 halogen functional group Chemical group 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 101150079595 Notch1 gene Proteins 0.000 description 2
- 230000035572 chemosensitivity Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- YCXIDNDPJQCJSR-UHFFFAOYSA-N 2-[5-methyl-6-(2-methylpyridin-4-yl)pyridin-3-yl]-n-(5-pyridin-2-ylpyridin-2-yl)acetamide Chemical compound C1=NC(C)=CC(C=2C(=CC(CC(=O)NC=3N=CC(=CC=3)C=3N=CC=CC=3)=CN=2)C)=C1 YCXIDNDPJQCJSR-UHFFFAOYSA-N 0.000 description 1
- DICRWYNNWVSVOE-UHFFFAOYSA-N 2-[6-(2-fluoropyridin-4-yl)-5-methylpyridin-3-yl]-n-(5-pyrazin-2-ylpyridin-2-yl)acetamide Chemical compound C=1N=C(C=2C=C(F)N=CC=2)C(C)=CC=1CC(=O)NC(N=C1)=CC=C1C1=CN=CC=N1 DICRWYNNWVSVOE-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 101000904539 Homo sapiens Probable E3 ubiquitin-protein ligase DTX3 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102000005650 Notch Receptors Human genes 0.000 description 1
- 108010070047 Notch Receptors Proteins 0.000 description 1
- 102000001756 Notch2 Receptor Human genes 0.000 description 1
- 108010029751 Notch2 Receptor Proteins 0.000 description 1
- 102100023992 Probable E3 ubiquitin-protein ligase DTX3 Human genes 0.000 description 1
- 102000044880 Wnt3A Human genes 0.000 description 1
- 108700013515 Wnt3A Proteins 0.000 description 1
- 238000003766 bioinformatics method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- WJQHZMSYJPODOP-UHFFFAOYSA-N n-[5-(3-fluorophenyl)pyridin-2-yl]-2-(5-methyl-6-pyridazin-4-ylpyridin-3-yl)acetamide Chemical group C=1N=C(C=2C=NN=CC=2)C(C)=CC=1CC(=O)NC(N=C1)=CC=C1C1=CC=CC(F)=C1 WJQHZMSYJPODOP-UHFFFAOYSA-N 0.000 description 1
- AXXNRMISICMFNS-UHFFFAOYSA-N n-[5-(4-acetylpiperazin-1-yl)pyridin-2-yl]-2-[6-(2-fluoropyridin-4-yl)-5-methylpyridin-3-yl]acetamide Chemical compound C1CN(C(=O)C)CCN1C(C=N1)=CC=C1NC(=O)CC1=CN=C(C=2C=C(F)N=CC=2)C(C)=C1 AXXNRMISICMFNS-UHFFFAOYSA-N 0.000 description 1
- FJFWSYCGKKNLDD-UHFFFAOYSA-N n-[5-(4-acetylpiperazin-1-yl)pyridin-2-yl]-2-[6-(2-methylpyridin-4-yl)-5-(trifluoromethyl)pyridin-3-yl]acetamide Chemical compound C1CN(C(=O)C)CCN1C(C=N1)=CC=C1NC(=O)CC(C=C1C(F)(F)F)=CN=C1C1=CC=NC(C)=C1 FJFWSYCGKKNLDD-UHFFFAOYSA-N 0.000 description 1
- 238000013517 stratification Methods 0.000 description 1
- 238000007482 whole exome sequencing Methods 0.000 description 1
- 101150068520 wnt3a gene Proteins 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361776334P | 2013-03-11 | 2013-03-11 | |
| US61/776,334 | 2013-03-11 | ||
| PCT/IB2014/059585 WO2014141038A2 (en) | 2013-03-11 | 2014-03-10 | Markers associated with wnt inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016513456A JP2016513456A (ja) | 2016-05-16 |
| JP2016513456A5 true JP2016513456A5 (enExample) | 2017-04-06 |
| JP6445984B2 JP6445984B2 (ja) | 2018-12-26 |
Family
ID=50382514
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015562469A Active JP6445984B2 (ja) | 2013-03-11 | 2014-03-10 | Ｗｎｔ阻害剤に関連するマーカー |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US10422007B2 (enExample) |
| EP (1) | EP2972372B1 (enExample) |
| JP (1) | JP6445984B2 (enExample) |
| KR (1) | KR102194746B1 (enExample) |
| CN (1) | CN105190313B (enExample) |
| AU (1) | AU2014229424B2 (enExample) |
| BR (1) | BR112015019567A8 (enExample) |
| CA (1) | CA2903976C (enExample) |
| CL (1) | CL2015002572A1 (enExample) |
| DK (1) | DK2972372T3 (enExample) |
| ES (1) | ES2681618T3 (enExample) |
| HU (1) | HUE039776T2 (enExample) |
| IL (1) | IL240794A (enExample) |
| MA (1) | MA38395B1 (enExample) |
| MX (1) | MX2015012534A (enExample) |
| PH (1) | PH12015501778A1 (enExample) |
| PL (1) | PL2972372T3 (enExample) |
| PT (1) | PT2972372T (enExample) |
| RU (2) | RU2663701C2 (enExample) |
| SG (1) | SG11201505873VA (enExample) |
| SI (1) | SI2972372T1 (enExample) |
| TN (1) | TN2015000325A1 (enExample) |
| TW (1) | TWI582239B (enExample) |
| WO (1) | WO2014141038A2 (enExample) |
| ZA (1) | ZA201505227B (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102015119552B4 (de) * | 2015-10-23 | 2022-06-15 | Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh | Monoterpenhaltige Zusammensetzung zur Behandlung von Tumor- und/oder Krebserkrankungen |
| CN105617359A (zh) * | 2015-12-31 | 2016-06-01 | 中国科学院成都生物研究所 | Wnt信号通路蛋白Frzb在制备抗肝癌药中的应用 |
| WO2017167150A1 (zh) * | 2016-03-31 | 2017-10-05 | 苏州云轩医药科技有限公司 | 一种3-氟吡啶杂环化合物及其应用 |
| CN106434968B (zh) * | 2016-11-18 | 2019-10-22 | 北京致成生物医学科技有限公司 | Ccdc168作为标记物在检测胰腺癌试剂中的应用 |
| TWI846703B (zh) | 2018-06-19 | 2024-07-01 | 日商武田藥品工業股份有限公司 | 癌症治療方法 |
| EP3833784A1 (en) * | 2018-08-07 | 2021-06-16 | PIQUR Therapeutics AG | Treatment of squamous cell carcinoma |
| US12195804B2 (en) | 2018-08-07 | 2025-01-14 | Board Of Regents, The University Of Texas System | Treatment of squamous cell carcinoma |
| EP4182479A1 (en) * | 2020-07-15 | 2023-05-24 | Université Libre de Bruxelles | Method for determining sensitivity to an antineoplastic agent |
| CN116808027B (zh) * | 2023-05-30 | 2025-08-29 | 重庆医科大学附属第一医院 | 化合物或其盐在制备抑制wnt7a基因活性的制剂中的应用 |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL154598B (nl) | 1970-11-10 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van laagmoleculire verbindingen en van eiwitten die deze verbindingen specifiek kunnen binden, alsmede testverpakking. |
| US3817837A (en) | 1971-05-14 | 1974-06-18 | Syva Corp | Enzyme amplification assay |
| US3939350A (en) | 1974-04-29 | 1976-02-17 | Board Of Trustees Of The Leland Stanford Junior University | Fluorescent immunoassay employing total reflection for activation |
| US3996345A (en) | 1974-08-12 | 1976-12-07 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
| US4277437A (en) | 1978-04-05 | 1981-07-07 | Syva Company | Kit for carrying out chemically induced fluorescence immunoassay |
| US4275149A (en) | 1978-11-24 | 1981-06-23 | Syva Company | Macromolecular environment control in specific receptor assays |
| US4366241A (en) | 1980-08-07 | 1982-12-28 | Syva Company | Concentrating zone method in heterogeneous immunoassays |
| US6040138A (en) | 1995-09-15 | 2000-03-21 | Affymetrix, Inc. | Expression monitoring by hybridization to high density oligonucleotide arrays |
| US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
| US5412087A (en) | 1992-04-24 | 1995-05-02 | Affymax Technologies N.V. | Spatially-addressable immobilization of oligonucleotides and other biological polymers on surfaces |
| US5578832A (en) | 1994-09-02 | 1996-11-26 | Affymetrix, Inc. | Method and apparatus for imaging a sample on a device |
| US5631734A (en) | 1994-02-10 | 1997-05-20 | Affymetrix, Inc. | Method and apparatus for detection of fluorescently labeled materials |
| DK1027437T3 (da) * | 1997-10-29 | 2008-11-24 | Genentech Inc | Anvendelse af det WNT-1 inducerede udskilte polypeptid WISP-1 |
| US6689744B2 (en) | 2000-09-22 | 2004-02-10 | Genentech, Inc. | Notch receptor agonists and uses |
| KR101126560B1 (ko) * | 2003-05-30 | 2012-04-05 | 도꾜 다이가꾸 | 약제 반응 예측 방법 |
| CN1852974A (zh) * | 2003-06-09 | 2006-10-25 | 密歇根大学董事会 | 用于治疗和诊断癌症的组合物和方法 |
| RU2392961C2 (ru) * | 2004-11-10 | 2010-06-27 | Хубрехт Лабораториум | Лечение аденомы и/или аденокарциномы кишечника с помощью ингибирования активации пути notch |
| JP2008535853A (ja) | 2005-04-07 | 2008-09-04 | ノバルティス ヴァクシンズ アンド ダイアグノスティクス インコーポレイテッド | 癌関連遺伝子 |
| WO2009074968A2 (en) * | 2007-12-12 | 2009-06-18 | Ecole Polytechnique Federale De Lausanne (Epfl) | Method for predicting the efficacy of cancer therapy |
| UA103918C2 (en) * | 2009-03-02 | 2013-12-10 | Айерем Элелси | N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as wnt signaling modulators |
| US20110212845A1 (en) | 2009-10-02 | 2011-09-01 | Denis Drygin | Biomarkers for predicting the sensitivity and response of protein kinase CK2-mediated diseases to CK2 Inhibitors |
| TWI535445B (zh) | 2010-01-12 | 2016-06-01 | 安可美德藥物股份有限公司 | Ｗｎｔ拮抗劑及治療和篩選方法 |
| KR20130043102A (ko) | 2010-04-01 | 2013-04-29 | 온코메드 파마슈티칼스, 인크. | 프리즐드-결합 작용제 및 그의 용도 |
| EP2549399A1 (en) | 2011-07-19 | 2013-01-23 | Koninklijke Philips Electronics N.V. | Assessment of Wnt pathway activity using probabilistic modeling of target gene expression |
-
2014
- 2014-03-07 TW TW103108007A patent/TWI582239B/zh not_active IP Right Cessation
- 2014-03-10 ES ES14712783.1T patent/ES2681618T3/es active Active
- 2014-03-10 CN CN201480014311.1A patent/CN105190313B/zh active Active
- 2014-03-10 RU RU2015138688A patent/RU2663701C2/ru active
- 2014-03-10 SI SI201430805T patent/SI2972372T1/sl unknown
- 2014-03-10 MX MX2015012534A patent/MX2015012534A/es unknown
- 2014-03-10 MA MA38395A patent/MA38395B1/fr unknown
- 2014-03-10 EP EP14712783.1A patent/EP2972372B1/en active Active
- 2014-03-10 KR KR1020157024490A patent/KR102194746B1/ko not_active Expired - Fee Related
- 2014-03-10 AU AU2014229424A patent/AU2014229424B2/en not_active Ceased
- 2014-03-10 SG SG11201505873VA patent/SG11201505873VA/en unknown
- 2014-03-10 JP JP2015562469A patent/JP6445984B2/ja active Active
- 2014-03-10 US US14/774,212 patent/US10422007B2/en active Active
- 2014-03-10 DK DK14712783.1T patent/DK2972372T3/en active
- 2014-03-10 HU HUE14712783A patent/HUE039776T2/hu unknown
- 2014-03-10 CA CA2903976A patent/CA2903976C/en active Active
- 2014-03-10 PT PT147127831T patent/PT2972372T/pt unknown
- 2014-03-10 RU RU2017141378A patent/RU2017141378A/ru not_active Application Discontinuation
- 2014-03-10 WO PCT/IB2014/059585 patent/WO2014141038A2/en not_active Ceased
- 2014-03-10 PL PL14712783T patent/PL2972372T3/pl unknown
- 2014-03-10 BR BR112015019567A patent/BR112015019567A8/pt not_active Application Discontinuation
-
2015
- 2015-07-20 ZA ZA2015/05227A patent/ZA201505227B/en unknown
- 2015-07-31 TN TN2015000325A patent/TN2015000325A1/en unknown
- 2015-08-12 PH PH12015501778A patent/PH12015501778A1/en unknown
- 2015-08-24 IL IL240794A patent/IL240794A/en active IP Right Grant
- 2015-09-10 CL CL2015002572A patent/CL2015002572A1/es unknown
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| Bi et al. | Effect of concurrent Chemoradiation with celecoxib vs concurrent Chemoradiation alone on survival among patients with non–small cell lung cancer with and without cyclooxygenase 2 genetic variants: a phase 2 randomized clinical trial | |
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