ES2505466T3 - Procedimientos para predecir la respuesta al tratamiento del cáncer de mama triple negativo - Google Patents
Procedimientos para predecir la respuesta al tratamiento del cáncer de mama triple negativo Download PDFInfo
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- ES2505466T3 ES2505466T3 ES11733335.1T ES11733335T ES2505466T3 ES 2505466 T3 ES2505466 T3 ES 2505466T3 ES 11733335 T ES11733335 T ES 11733335T ES 2505466 T3 ES2505466 T3 ES 2505466T3
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- 238000011282 treatment Methods 0.000 title abstract description 8
- 230000004044 response Effects 0.000 title abstract description 5
- 238000000034 method Methods 0.000 title abstract description 4
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 title description 5
- 208000022679 triple-negative breast carcinoma Diseases 0.000 title description 5
- 206010006187 Breast cancer Diseases 0.000 abstract description 7
- 208000026310 Breast neoplasm Diseases 0.000 abstract description 7
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 abstract description 5
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 abstract description 5
- 229940120638 avastin Drugs 0.000 abstract description 3
- 229960000397 bevacizumab Drugs 0.000 abstract description 3
- 229960004562 carboplatin Drugs 0.000 abstract description 3
- 190000008236 carboplatin Chemical compound 0.000 abstract description 3
- 239000002246 antineoplastic agent Substances 0.000 abstract 3
- 229940041181 antineoplastic drug Drugs 0.000 abstract 3
- 210000004027 cell Anatomy 0.000 abstract 3
- 229930012538 Paclitaxel Natural products 0.000 abstract 1
- 230000002934 lysing effect Effects 0.000 abstract 1
- 229960001592 paclitaxel Drugs 0.000 abstract 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound 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 RCINICONZNJXQF-MZXODVADSA-N 0.000 abstract 1
- 210000004881 tumor cell Anatomy 0.000 abstract 1
- 230000004913 activation Effects 0.000 description 6
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 5
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 5
- 238000003018 immunoassay Methods 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 3
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 3
- 102000038030 PI3Ks Human genes 0.000 description 2
- 108091007960 PI3Ks Proteins 0.000 description 2
- 229940028652 abraxane Drugs 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000013188 needle biopsy Methods 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000017891 HER2 positive breast carcinoma Diseases 0.000 description 1
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 1
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 1
- 102220497176 Small vasohibin-binding protein_T47D_mutation Human genes 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- -1 c-KIT Proteins 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
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- 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
- G01N33/57407—Specifically defined cancers
- G01N33/57415—Specifically defined cancers of breast
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/71—Assays involving receptors, cell surface antigens or cell surface determinants for growth factors; for growth regulators
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- 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
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- 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
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Abstract
Un procedimiento para predecir la respuesta de un tumor de mama triple negativo al tratamiento con un fármaco antineoplásico, comprendiendo el procedimiento : (a) lisar una célula tumoral obtenida del tumor de mama triple negativo para producir un extracto celular; (b) determinar el nivel de expresión de VEGFR2 en el extracto celular; y (c) comparar el nivel de expresión de VEGFR2 en el extracto celular determinado en la etapa (b) con un nivel de expresión de VEGFR2 de referencia, en el que la presencia de un nivel de expresión de VEGFR2 bajo en comparación con la referencia es un factor pronóstico de la respuesta al tratamiento con el fármaco antineoplásico, en el que el fármaco antineoplásico es una combinación de bevacizumab (Avastin®), carboplatino y paclitaxel.
Description
E11733335
19-09-2014
Tabla 2. Identificación de tejido de cáncer de mama con ERBB2.
20520 3 >2x10e6 113.161 3.687
26379
KW7VHAET
1 -3.367 36
21704 3 1.520,673 48.669 93
WUQT6
2 314.653 17.864 47
NP11802
1 -2.053 17
26811 3 >2x10e6 307.337 4.523
25882
2 219.387 3.026 39
19898
1 -894 -
26106 3 >2x10e6 125.062 935
25798
2 137.399 10.424 248
21655
1 137.941 11.983 65
22080 3 1.340,073 142.055 2.215
24960
2 -15.563 43
24676
1 -2.905 -
19844 3 956,628 49.042 158
26154
2 110.091 3.511 111
9895
1 -8.896 214
20371 3 >2x10e6 105.413 728
25061
2 -8.993 105
19692
1 -2.664 50
AUBBG 3 486,835 15.525 56
22176
2 -3.788 95
17253
0 ---
22715 3 1.148,445 58.781 3.467
21962
2 -1.515 102
20007
0 -5.536 52
21703 3 643.263 31.597 92
24708
2 -4.769 16
21603
0 -4.463 44
19927 3 1.452,313 91.566 563
20525
2 -1.806 50
1R2117
0 --66
20330 3 458,839 45.080 1.251
24916
2 -2.224 15
0
Las imágenes de matrices CEER ilustrativas para las muestras subrayadas se muestran en la figura 6 y la IPtransferencia de bandas de tipo Western para las muestras recuadradas se muestran en la figura 7. Los valores de RTK/célula se determinan por comparación de la cantidad de muestras de entrada y la cantidad equivalente de células BT474 de referencia.
Tabla 3. Análisis de t-ERBB2 para muestras de AAF.
- ID de la muestra
- t-ERBB2 (RTK/célula) Pt-ERBB2 (pRTK/célula)
- 8C3-002-001
- 57,341 3,062
- 8C3-005-006
- 26,989 5,309
- 8C3-005-007
- 50,741 5,204
10 Como se muestra en la figura 8, en 174 muestras de cáncer de mama se observó la expresión y la activación de proteínas de una amplia variedad de rutas. La muestra con la señal más alta para cada marcador se indica con el color más oscuro. El CEER-HER2 mostró una alta correlación con el estado de IHQ-HER2. El estado de HER2 discordante entre el CEER y la IHQ se resolvió por IP-transferencia de bandas Western y mostró una correlación de
15 >98 %. El nivel de HER3-P mostró un grado de correlación alto con la activación de HER3-T y PI3K. El perfil de cMET también mostró una fuerte correlación con la activación de PI3K. El 27 % (12/45 de 2+ por IHQ) y el 21 % (11/53 de 0/1+ por IHQ) de los tejidos con cáncer de mama con niveles no sobreexpresados, pero sí significativos, de HER2 mostraron una fosforilación de más del 5 % del receptor HER2 expresado.
20 Conclusión
El estado de HER2 y sus formas variantes, así como otras RTK, proporciona información fundamental sobre los posibles mecanismos de los pacientes con cáncer de mama positivo para HER2 que no responden al trastuzumab debido a su resistencia primaria o adquirida. Se puede utilizar el análisis CEER descrito en el presente documento
25 para identificar en pacientes con cáncer de mama las proteínas de transducción de señales para seleccionar un tratamiento dirigido adecuado.
Ejemplo 5. Identificación integral de rutas para predecir la respuesta al tratamiento en el cáncer de mama triple negativo metastásico (CMTNM).
30 En el CMTN, se necesitan mejores tratamientos y marcadores pronósticos. En este estudio se usaron piezas de biopsia con aguja gruesa de pacientes con cáncer de mama triple negativo tratados con B (Avastin® [bevacizumab]), C (carboplatino) y nabP (Abraxane®) ("tratamiento triple") para (1) determinar el nivel de expresión y el grado de activación de diversas proteínas de rutas de señalización en CMTNM (p. ej., VEGFR2, c-KIT, HER1, etc.) y (2)
35 correlacionar estos patrones de expresión y activación del CMTNM con la respuesta.
Se recogieron piezas de biopsia con aguja gruesa de cáncer de mama triple negativo (n=17) obtenidas de pacientes antes de comenzar el tratamiento con B (Avastin® [bevacizumab]), C (carboplatino) y nabP (Abraxane®) y se congelaron adecuadamente a -80 °C. Se aplicó un procedimiento de inmunoensayo novedoso para estudiar los 40 niveles de expresión y el grado de activación de proteínas de señalización en de 1000ng a 5000ng de tejidos congelados. El inmunoensayo colaborativo reactivo potenciado por enzimas (CEER) (también conocido como el inmunoensayo colaborativo de proximidad (COPIA)) como se describe en el presente documento es una plataforma de inmunomicromatrices múltiple que utiliza la formación de un inmunocomplejo exclusivo que requiere la colocalización de dos anticuerpos detectores para canalizar acontecimientos para lograr la generación/amplificación 45 de la señal que da lugar a una sensibilidad analítica y una especificidad extremadamente altas. La figura 9 proporciona un ejemplo de identificación funcional de rutas por CEER en una muestra de cáncer de mama triple negativo obtenida por biopsia por punción con aguja gruesa en comparación con células de cáncer de mama T47D
33
Claims (1)
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imagen1 imagen2
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29443310P | 2010-01-12 | 2010-01-12 | |
| US294433P | 2010-01-12 | ||
| US32562410P | 2010-04-19 | 2010-04-19 | |
| US325624P | 2010-04-19 | ||
| US32860210P | 2010-04-27 | 2010-04-27 | |
| US328602P | 2010-04-27 | ||
| US35183810P | 2010-06-04 | 2010-06-04 | |
| US351838P | 2010-06-04 | ||
| PCT/US2011/021026 WO2011088149A2 (en) | 2010-01-12 | 2011-01-12 | Methods for predicting response of triple-negative breast cancer to therapy |
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| Publication Number | Publication Date |
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| ES2505466T3 true ES2505466T3 (es) | 2014-10-10 |
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| ES11733335.1T Active ES2505466T3 (es) | 2010-01-12 | 2011-01-12 | Procedimientos para predecir la respuesta al tratamiento del cáncer de mama triple negativo |
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| US (2) | US9488654B2 (es) |
| EP (1) | EP2524232B1 (es) |
| JP (1) | JP5764144B2 (es) |
| KR (1) | KR20120115390A (es) |
| CN (1) | CN102822676B (es) |
| AU (1) | AU2011205343B2 (es) |
| BR (1) | BR112012017084A2 (es) |
| CA (1) | CA2787225A1 (es) |
| ES (1) | ES2505466T3 (es) |
| IL (1) | IL220833A0 (es) |
| MX (1) | MX2012008153A (es) |
| NZ (1) | NZ601348A (es) |
| RU (1) | RU2558931C2 (es) |
| WO (1) | WO2011088149A2 (es) |
| ZA (1) | ZA201206019B (es) |
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| RU2341198C2 (ru) * | 2006-11-27 | 2008-12-20 | ФГУ Ростовский научно-исследовательский онкологический институт Росздрава | Способ оценки ангиогенных факторов при химиотерапии рака молочной железы |
| US20100092485A1 (en) * | 2007-01-18 | 2010-04-15 | University Of Southern California | Genetic Markers for Predicting Responsiveness to Combination Therapy |
| US20110306572A1 (en) * | 2007-09-24 | 2011-12-15 | Tragara Pharmaceuticals, Inc | COMBINATION THERAPY FOR THE TREATMENT OF CANCER USING COX-2 INHIBITORS AND DUAL InHIBITORS OF EGFR [ErbB1] AND HER-2 [ErbB2] |
| NZ617520A (en) | 2008-02-25 | 2015-05-29 | Nestec Sa | Drug selection for breast cancer therapy using antibody-based arrays |
| US8071315B2 (en) * | 2008-04-30 | 2011-12-06 | Sanford-Burnham Medical Research Institute | Detecting Bcl-B expression in cancer and uses thereof |
| AU2010248884B2 (en) | 2009-05-14 | 2015-04-02 | Nestec S.A. | Biomarkers for determining sensitivity of breast cancer cells to HER2-targeted therapy |
| MX343801B (es) * | 2010-07-19 | 2016-11-23 | F Hoffmann-La Roche Ag * | Biomarcadores de plasma de sangre para terapias de combinacion con bevacizumab para tratamiento de cancer de mama. |
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|---|---|
| CA2787225A1 (en) | 2011-07-21 |
| CN102822676A (zh) | 2012-12-12 |
| JP5764144B2 (ja) | 2015-08-12 |
| EP2524232A4 (en) | 2013-06-12 |
| IL220833A0 (en) | 2012-08-30 |
| WO2011088149A2 (en) | 2011-07-21 |
| BR112012017084A2 (pt) | 2016-04-12 |
| US9488654B2 (en) | 2016-11-08 |
| CN102822676B (zh) | 2015-02-18 |
| US20170227542A1 (en) | 2017-08-10 |
| WO2011088149A3 (en) | 2011-10-27 |
| EP2524232A2 (en) | 2012-11-21 |
| NZ601348A (en) | 2014-07-25 |
| RU2012134390A (ru) | 2014-02-20 |
| AU2011205343B2 (en) | 2015-08-13 |
| RU2558931C2 (ru) | 2015-08-10 |
| US20130012407A1 (en) | 2013-01-10 |
| KR20120115390A (ko) | 2012-10-17 |
| JP2013517461A (ja) | 2013-05-16 |
| US10697967B2 (en) | 2020-06-30 |
| EP2524232B1 (en) | 2014-08-06 |
| MX2012008153A (es) | 2012-11-06 |
| AU2011205343A1 (en) | 2012-08-02 |
| HK1178602A1 (en) | 2013-09-13 |
| ZA201206019B (en) | 2015-06-24 |
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