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USE OF TREFOIL FACTOR FAMILY 3 (TFF3) IN THE PROGNOSIS OF PATIENTS DIAGNOSED WITH COLORECTAL CANCERCM Patents

Índice de la ficha

Updated at
24/07/2026
Numero publicacion
EP.2236625.A1
Fecha publicacion
06/10/2010
Numero solicitud
EP20080855888
Fecha presentacion
04/12/2008

En detalle

Resumen

The invention relates to in vitro methods for establishing a prognosis concerning the course of a patient diagnosed with colorectal cancer following the administration of a therapy, monitoring the effect of said therapy on the patient or predicting the clinical response of the patient to the therapy in terms of basal expression levels. Said methods comprise the quantification of the expression level of the TFF3 gene or the protein encoded by said gene.

Reivindicaciones

1. An in vitro method for establishing a prognosis concerning the progress of a patient diagnosed with colorectal cancer after the administration of a therapy, comprising (i) quantifying the expression levels of the TFF3 gene or (ii) quantifying the expression levels of the protein encoded by said gene, or any functionally equivalent variant of said TFF3 protein, in a biological sample from said patient before and after the therapy, wherein an increase of the expression of TFF3 or of the expression level of the protein encoded by said gene, or of any functionally equivalent variant of said TFF3 protein, after the administered therapy with respect to the expression of TFF3 or the expression level of the protein encoded by said gene, or any functionally equivalent variant of said TFF3 protein, before the therapy, is indicative of a worse progress of the patient. 2. The method according to claim 1, wherein the parameter indicating the progress of a patient diagnosed with colorectal cancer is selected from the group of risk of relapse, disease-free survival and/or overall survival of the patient. 3. An in vitro method for monitoring the effect of a therapy administered to a patient diagnosed with colorectal cancer, comprising (i) quantifying the expression levels of the TFF3 gene or (ii) quantifying the levels of the protein encoded by said gene, or any functionally equivalent variant of said TFF3 protein, in a biological sample from said patient before and after said therapy, wherein an increase of the expression of TFF3 or of the expression level of the protein encoded by said gene, or of any functionally equivalent variant of said TFF3 protein, after the administered therapy with respect to the expression of TFF3 or the expression level of the protein encoded by said gene, or any functionally equivalent variant of said TFF3 protein, before the therapy, is indicative that the administered therapy is not effective. 4. An in vitro method for designing a customized therapy for a patient diagnosed with colorectal cancer, comprising (i) quantifying the expression levels of the TFF3 gene or (ii) quantifying the levels of the protein encoded by said gene, or any functionally equivalent variant of said TFF3 protein, in a biological sample from said patient before and after the therapy, wherein an increase of the expression of TFF3 or of the expression level of the protein encoded by said gene, or of any functionally equivalent variant of said TFF3 protein, after the administered therapy with respect to the expression of TFF3 or the expression level of the protein encoded by said gene, or any functionally equivalent variant of said TFF3 protein, before the therapy, is indicative that the patient needs an alternative therapy to the therapy originally administered. 5. The method according to any of claims 1 to 4, wherein quantifying the expression levels of the TFF3 gene comprises quantifying the messenger RNA (mRNA) of the TFF3 gene, a fragment of said mRNA, complementary DNA (cDNA) of the TFF3 gene, a fragment of said cDNA, or mixtures thereof. 6. The method according to any of claims 1 to 5, wherein the expression levels of the TFF3 gene are quantified by means of a quantitative polymerase chain (PCR) reaction. 7. The method according to any of claims 1 to 5, wherein quantifying the levels of the protein encoded by the TFF3 gene comprises quantifying the TFF3 protein. 8. The method according to claim 7, wherein the levels of protein encoded by the TFF3 gene are quantified by means of western blot, immunohistochemistry or ELISA. 9. The method according to any of claims 1 to 8, wherein the administered therapy is a cytotoxic and/or cytostatic treatment. 10. The method according to claim 9, wherein the cytotoxic and/or cytostatic treatment is chemotherapy, radiotherapy, antitumor agents or combinations thereof. 11. The method according to claim 10, wherein the chemotherapy comprises a compound selected from an alkylating agent preventing replication, a fluoropyrimidine, a thymidylate synthase inhibitor, a topoisomerase inhibitor and combinations thereof. 12. The method according to claim 11, wherein the alkylating agent preventing replication is oxaliplatin, the fluoropyrimidine is 5-fluorouracil, UFT, Utefos or capecitabine, the thymidylate synthase inhibitor is raltitrexed and the topoisomerase I inhibitor is irinotecan. 13. The method according to claim 10, wherein the antitumor agents comprise antiangiogenic agents and signaling pathway inhibitors. 14. The method according to claim 13, wherein the antiangiogenic agent is bevacizumab and the signaling pathway inhibitor is cetuximab, panitumumab, or erlotinib. 15. The method according to any of claims 1 to 14, wherein the biological sample is a tissue sample or a biological fluid. 16. The method according to claim 15, wherein the tissue sample is tumor tissue sample. 17. The method according to any of claims 1 to 16, wherein the colorectal cancer is large intestine adenocarcinoma in stages II or III or IV. 18. An in vitro method for establishing a prognosis concerning the progress of a patient diagnosed with colorectal cancer, comprising determining the distribution pattern of the protein encoded by the TFF3 gene, or any functionally equivalent variant of said TFF3 protein, in the tumor, wherein the detection of TFF3, or any functionally equivalent variant of said TFF3 protein, in the lumen of the tumor microglands and/or inside the lymph or blood vessels is indicative of a worse progress of a patient. 19. The method according to claim 18, wherein the parameter indicating the progress of a patient diagnosed with colorectal cancer is selected from the group of risk of relapse, disease-free survival and/or overall survival of the patient. 20. The method according to claim 18 or 19, wherein the chemoradiotherapy has been administered to the patient diagnosed with colorectal cancer before the extraction of the tumor. 21. The method according to claim 18 or 20, wherein the detection of the protein encoded by the TFF3 gene is performed by means of immunohistochemistry. 22. The method according to any of claims 18 to 21, wherein the colorectal cancer is large intestine adenocarcinoma in stages II or III or IV. 23. A method for predicting the clinical response of a patient diagnosed with colorectal cancer to a therapy, comprising (i) quantifying the expression levels of the TFF3 gene or (ii) quantifying the expression levels of the protein encoded by said gene, or any functionally equivalent variant of said TFF3 protein, in a biological sample from said patient before the administration of the therapy, wherein elevated expression levels of TFF3 with respect to the basal expression levels of TFF3 are indicative of a poor clinical response of the patient to the therapy.

Etiquetas

Inventores
Casado Saenz EnriqueCejas Guerrero PalomaSanchez Hernandez Jose JavierGonzalez Baron ManuelPerona Abellon RosarioSanchez Hernandez José Javier
Solicitantes
Universidad Autónoma de MadridFundación Para la Investigación Biomédica del Hospital Universitario de la PazConsejo Superior de Investigaciones CientíficasConsejo Superior de Investigaciones CientíficasesCasado Saenz EnriqueCejas Guerrero PalomaSanchez Hernandez Jose JavierGonzalez Baron ManuelPerona Abellon Rosario
Clasificacion ipc
A61B 5/ 00 A IC12Q 1/ 68 A IG01N 33/ 50 A I
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