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METHOD FOR PREDICTING THE RESPONSE TO TREATMENT WITH RADIOTHERAPY COMBINED WITH CHEMOTHERAPY BASED ON CISPLATINCM Patents

Índice de la ficha

Updated at
24/07/2026
Numero publicacion
EP.3006572.A1
Fecha publicacion
13/04/2016
Numero solicitud
EP20140804898
Fecha presentacion
27/05/2014

En detalle

Resumen

[0001] The invention relates to a method for predicting the response to treatment with radiotherapy combined with chemotherapy based on cisplatin in patients suffering from cancer, preferably non-small cell lung cancer, where said method is based on the detection of the presence of methylation of the gene IGFBP-3. The invention also relates to an in vitro method for designing a personalised treatment for an individual suffering from said disease. The method of the invention can be quantitative or semi-quantitative. The invention also relates to a probe for the quantitative detection of the methylation of the gene IGFBP-3, to a kit comprising same, and to the use of said kit for predicting the response of an individual receiving the described treatment..

Reivindicaciones

1. Method to obtain useful data to predict the response of a subject with cancer to treatment with radiotherapy combined with cisplatin-based chemotherapy, which comprises detecting and/or quantifying the promoter methylation of theIGFBP-3 gene in a biological sample from said subject. 2. In vitro method to design an individualised treatment for a subject with cancer, which comprises detecting and/or quantifying the promoter methylation of theIGFBP-3 gene in a biological sample from said subject, wherein the presence of methylation in said promoter is indicative that the treatment to be administered is radiotherapy combined with cisplatin-based chemotherapy. 3. Method according to any one of claims 1 or 2, wherein the detection and/or quantification of the promoter methylation of theIGFBP-3 gene is performed in the promoter region, between positions -584 and -492 of the promoter, both included. 4. Method according to any one of claims 1 to 3, wherein the detection and/or quantification of the promoter methylation of theIGFBP-3 gene are performed at positions -532 and -526 of the promoter. 5. Method according to any one of claims 1 to 4, wherein the detection and/or quantification of the promoter methylation of theIGFBP-3 gene are performed by means of a polymerase chain reaction. 6. Method according to claim 5, wherein the polymerase chain reaction comprises using the primer pairs SEQ ID NO: 3 and SEQ ID NO: 4, and/or SEQ ID NO: 5 and SEQ ID NO: 6. 7. Method according to claim 6, wherein the polymerase chain reaction comprises using the primer pair SEQ ID NO: 3 and SEQ ID NO: 4. 8. Method according to any of claims 6 or 7, wherein a nucleic acid probe is further used which comprises nucleotide sequence SEQ ID NO: 7. 9. Method according to claim 8, wherein the probe is nucleotide sequence SEQ ID NO: 7. 10. Method according to any of claims 8 or 9, wherein the probe comprises a fluorophore at the amino-terminal end and/or at the carboxy-terminal end. 11. In vitro method to predict the response of a subject with cancer to treatment with radiotherapy combined with cisplatin-based chemotherapy, comprising the following steps: a. isolation of deoxyribonucleic acid in a biological sample isolated from a subject; b. modification of the isolated deoxyribonucleic acid by means of sodium bisulfite; c. hybridisation using specific primers; d. amplification of a sequence located between the primers described in step (c); e. detection of the promoter methylation of theIGFBP-3 gene; f. comparing the methylation of step (d) with standard levels; g. finding significant differences in the comparison of step (f); h. associating the significant differences of step (g) with a promoter methylation or demethylation of theIGFBP-3 gene; i. associating the presence of methylation of step (h) with a favourable response to treatment with radiotherapy combined with cisplatin-based chemotherapy; or associating the demethylation of step (h) with an unfavourable response to treatment with radiotherapy combined with cisplatin-based chemotherapy. 12. Method according to claim 11, wherein the primers of step (c) are the primer pairs SEQ ID NO: 3 and SEQ ID NO: 4, and/or SEQ ID NO: 5 and SEQ ID NO: 6. 13. Method according to claim 12, wherein the primers of step (c) are SEQ ID NO: 3 and SEQ ID NO: 4. 14. Method according to any of claims 11 to 13, further comprising a probe in step (c) and quantifying the methylation of step (e). 15. Method according to claim 14, wherein the probe comprises nucleotide sequence SEQ ID NO: 7. 16. Method according to claim 15, wherein the probe is nucleotide sequence SEQ ID NO: 7. 17. Method according to any of claims 1 to 16, wherein the subject has lung cancer, ovarian cancer, head and neck cancer, glioma or breast cancer. 18. Method according to claim 17, wherein the lung cancer is non-microcytic lung cancer. 19. Method according to any of claims 1 to 18, wherein the biological sample is selected from the group consisting of tissue, blood, plasma, serum, lymph, broncho-alveolar lavage, saliva, urine or ascitic fluid. 20. Method according to any of claims 1 to 19, wherein the biological sample is fresh, frozen, fixed or fixed and embedded in paraffin. 21. Nucleic acid probe which comprises nucleotide sequence SEQ ID NO: 7. 22. Nucleic acid probe which is nucleotide sequence SEQ ID NO: 7. 23. Probe according to any of claims 21 to 22, further comprising a fluorophore at the amino-terminal end and/or at the carboxy-terminal end. 24. In vitro use of a probe according to any of claims 21 to 23, to detect and/or quantify the promoter methylation of theIGFBP-3 gene in a biological sample from a subject. 25. In vitro use of a probe according to any of claims 21 to 24, to determine the response of a subject to treatment with radiotherapy combined with cisplatin-based chemotherapy. 26. Use according to any of claims 24 or 25, wherein the subject has cancer. 27. Use according to claim 26, wherein the cancer is lung cancer, ovarian cancer, head and neck cancer, glioma or breast cancer. 28. Use according to claim 27, wherein the lung cancer is non-microcytic lung cancer. 29. Use according to any of claims 24 to 28, wherein the biological sample is selected from the group consisting of tissue, blood, plasma, serum, lymph, broncho-alveolar lavage, saliva, urine or ascitic fluid. 30. Use according to any of claims 24 to 29, wherein the biological sample is fresh, frozen, fixed or fixed and embedded in paraffin. 31. Kit which comprises a probe according to any of claims 21 to 23. 32. Kit according to claim 31, which further comprises primers. 33. Kit according to claim 32, wherein the primers are the primer pairs SEQ ID NO: 3 and SEQ ID NO: 4, and/or SEQ ID NO: 5 and SEQ ID NO: 6. 34. In vitro use of the kit according to any of claims 31 to 33, to determine and/or quantify the promoter methylation of theIGFBP-3 gene in a biological sample from a subject. 35. In vitro use of the kit according to claim 34, to predict the response of a subject to treatment with radiotherapy combined with cisplatin-based chemotherapy. 36. Use according to any of claims 34 or 35, wherein the subject has cancer. 37. Use according to claim 36, wherein the cancer is lung cancer, ovarian cancer, head and neck cancer, glioma or breast cancer. 38. Use according to claim 37, wherein the lung cancer is non-microcytic lung cancer.

Etiquetas

Inventores
Ibáñez de Cáceres InmaculadaBelda Iniesta CristóbalPernía Arias OlgaPerona Abellón RosarioCortés Sempere MaríaIbanez de Caceres InmaculadaBelda Iniesta CristobalPernia Arias OlgaPerona Abellon RosarioCortes Sempere MariaCortes Sempere MaríaCortés Sempere Maria
Solicitantes
Fundación Para la Investigación Biomédica del Hospital Universitario de la PazConsejo Superior de Investigaciones CientíficasUniversidad Autónoma de MadridFundación Hospital de MadridFundación Para la Investigación Biomédica del Hospital Univ de la PazConsejo Superior de Investig Científicas
Clasificacion ipc
C12Q 1/ 6886 A IC12Q 1/ 68 A IC07H 21/ 02 A IC07H 21/ 04 A I
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