Preclinical validation of an aptamer-based formulation against MNK1 as an antitumour therapy in breast cancer. (Q3178272): Difference between revisions
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(Removed claim: summary (P836): Breast cancer is one of the most commonly diagnosed cancers in women. The PI3K/AKT/mTOR signalling route is among the most frequently deregulated mechanisms in patients with this type of cancer. Due to the importance of this route, kinases of this route have been used as therapeutic targets and pharmacological inhibitors of them have been identified. MNKs kinase proteins, which belong to the MAPK pathway, are phosphorylated and activated by...) |
(Created claim: summary (P836): Breast cancer is one of the most commonly diagnosed cancers in women. The PI3K/AKT/mTOR signalling route is among the most frequently deregulated mechanisms in patients with this type of cancer. Due to the importance of this route, kinases of this route have been used as therapeutic targets and pharmacological inhibitors of them have been identified. MNKs kinase proteins, which belong to the MAPK pathway, are phosphorylated and activated by E...) |
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Breast cancer is one of the most commonly diagnosed cancers in women. The PI3K/AKT/mTOR signalling route is among the most frequently deregulated mechanisms in patients with this type of cancer. Due to the importance of this route, kinases of this route have been used as therapeutic targets and pharmacological inhibitors of them have been identified. MNKs kinase proteins, which belong to the MAPK pathway, are phosphorylated and activated by ERK1/2 and p38MAPK and phosphorylan eIF4E. Recently, results supporting the role of eIF4E phosphorylation in tumorogenesis have been published. Although some studies point to eIF4E as a therapeutic target, the fact that this factor has a fundamental biological role in protein synthesis in normal cells is an obstacle to these strategies. On the other hand, overexpression of MNK1 in breast tumors suggests that this protein could be an antitumor potential target. Thus pharmacological inhibitors directed against MNK1 appear to provide an effective and non-harmful anti-tumoral strategy for non-tumour cells. Several studies have shown that the combination of MNKs and mTOR inhibitors increases the antitumor response by inhibiting cell proliferation and inducing apoptosis, relative to the effect obtained with monotherapy. The aim of the project is to obtain a formulation based on a specific aptamer against the kinase MNK1 for application, as monotherapy, combination therapy or replacement therapy, in the treatment of breast cancer. To this end, ApMNKQ2 aptámer, which has already demonstrated antitumor capacity in vitro using breast cancer cell lines, will be conjugated with magnetic nanoparticles (NPM) in order to direct the drug towards the tumor under systemic administration, increasing its effectiveness, protecting against degradation and reducing its toxicity. (English) | |||||||||||||||
| Property / summary: Breast cancer is one of the most commonly diagnosed cancers in women. The PI3K/AKT/mTOR signalling route is among the most frequently deregulated mechanisms in patients with this type of cancer. Due to the importance of this route, kinases of this route have been used as therapeutic targets and pharmacological inhibitors of them have been identified. MNKs kinase proteins, which belong to the MAPK pathway, are phosphorylated and activated by ERK1/2 and p38MAPK and phosphorylan eIF4E. Recently, results supporting the role of eIF4E phosphorylation in tumorogenesis have been published. Although some studies point to eIF4E as a therapeutic target, the fact that this factor has a fundamental biological role in protein synthesis in normal cells is an obstacle to these strategies. On the other hand, overexpression of MNK1 in breast tumors suggests that this protein could be an antitumor potential target. Thus pharmacological inhibitors directed against MNK1 appear to provide an effective and non-harmful anti-tumoral strategy for non-tumour cells. Several studies have shown that the combination of MNKs and mTOR inhibitors increases the antitumor response by inhibiting cell proliferation and inducing apoptosis, relative to the effect obtained with monotherapy. The aim of the project is to obtain a formulation based on a specific aptamer against the kinase MNK1 for application, as monotherapy, combination therapy or replacement therapy, in the treatment of breast cancer. To this end, ApMNKQ2 aptámer, which has already demonstrated antitumor capacity in vitro using breast cancer cell lines, will be conjugated with magnetic nanoparticles (NPM) in order to direct the drug towards the tumor under systemic administration, increasing its effectiveness, protecting against degradation and reducing its toxicity. (English) / rank | |||||||||||||||
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| Property / summary: Breast cancer is one of the most commonly diagnosed cancers in women. The PI3K/AKT/mTOR signalling route is among the most frequently deregulated mechanisms in patients with this type of cancer. Due to the importance of this route, kinases of this route have been used as therapeutic targets and pharmacological inhibitors of them have been identified. MNKs kinase proteins, which belong to the MAPK pathway, are phosphorylated and activated by ERK1/2 and p38MAPK and phosphorylan eIF4E. Recently, results supporting the role of eIF4E phosphorylation in tumorogenesis have been published. Although some studies point to eIF4E as a therapeutic target, the fact that this factor has a fundamental biological role in protein synthesis in normal cells is an obstacle to these strategies. On the other hand, overexpression of MNK1 in breast tumors suggests that this protein could be an antitumor potential target. Thus pharmacological inhibitors directed against MNK1 appear to provide an effective and non-harmful anti-tumoral strategy for non-tumour cells. Several studies have shown that the combination of MNKs and mTOR inhibitors increases the antitumor response by inhibiting cell proliferation and inducing apoptosis, relative to the effect obtained with monotherapy. The aim of the project is to obtain a formulation based on a specific aptamer against the kinase MNK1 for application, as monotherapy, combination therapy or replacement therapy, in the treatment of breast cancer. To this end, ApMNKQ2 aptámer, which has already demonstrated antitumor capacity in vitro using breast cancer cell lines, will be conjugated with magnetic nanoparticles (NPM) in order to direct the drug towards the tumor under systemic administration, increasing its effectiveness, protecting against degradation and reducing its toxicity. (English) / qualifier | |||||||||||||||
point in time: 12 October 2021
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Revision as of 18:57, 12 October 2021
Project Q3178272 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | Preclinical validation of an aptamer-based formulation against MNK1 as an antitumour therapy in breast cancer. |
Project Q3178272 in Spain |
Statements
43,000.0 Euro
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86,000.0 Euro
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50.0 percent
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1 January 2019
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30 September 2021
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FUNDACION INVESTIGACION BIOMEDICA HOSPITAL RAMON Y CAJAL
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40°25'0.12"N, 3°42'12.89"W
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28079
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El cáncer de mama es uno de los cánceres más comúnmente diagnosticados en las mujeres. La ruta de señalización PI3K/AKT/mTOR está entre los mecanismos más frecuentemente desregulado en pacientes con este tipo de cáncer. Debido a la importancia de esta vía, las quinasas de esta ruta se han utilizado como dianas terapéuticas y se han identificado inhibidores farmacológicos de las mismas. Las proteínas quinasas MNKs, que pertenecen a la vía de las MAPK, son fosforiladas y activadas por ERK1/2 y p38MAPK y fosforilan al eIF4E. Recientemente se han publicado resultados que apoyan el papel de la fosforilación de eIF4E en la tumorogénesis. Aunque algunos estudios apuntan a eIF4E como diana terapéutica, el hecho de que este factor tenga un papel biológico fundamental en la síntesis de proteínas en células normales es un obstáculo para estas estrategias. Por otra parte, la sobreexpresión de MNK1 en tumores de mama sugiere que esta proteína podría ser una potencial diana antitumoral. Así inhibidores farmacológicos dirigidos contra MNK1 parecen proporcionar una estrategia anti-tumoral efectiva y no perjudicial para las células no tumorales. Varios estudios han demostrado que la combinación de inhibidores de MNKs y mTOR aumenta la respuesta antitumoral inhibiendo la proliferación celular e induciendo apoptosis, respecto al efecto obtenido con la monoterapia. El objetivo del proyecto es obtener una formulación basada en un aptámero específico frente a la quinasa MNK1 para su aplicación, en monoterapia, terapia combinada o terapia sustitutiva, en el tratamiento del cáncer de mama. Para ello, el aptámero ApMNKQ2, que ya ha demostrado capacidad antitumoral in vitro utilizando líneas celulares de cáncer de mama, será conjugado con nanopartículas magnéticas (NPM) con el objeto de dirigir al fármaco hacia el tumor en administración sistémica, aumentando su eficacia, protegiendo frente a degradación y disminuyendo su toxicidad. (Spanish)
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Breast cancer is one of the most commonly diagnosed cancers in women. The PI3K/AKT/mTOR signalling route is among the most frequently deregulated mechanisms in patients with this type of cancer. Due to the importance of this route, kinases of this route have been used as therapeutic targets and pharmacological inhibitors of them have been identified. MNKs kinase proteins, which belong to the MAPK pathway, are phosphorylated and activated by ERK1/2 and p38MAPK and phosphorylan eIF4E. Recently, results supporting the role of eIF4E phosphorylation in tumorogenesis have been published. Although some studies point to eIF4E as a therapeutic target, the fact that this factor has a fundamental biological role in protein synthesis in normal cells is an obstacle to these strategies. On the other hand, overexpression of MNK1 in breast tumors suggests that this protein could be an antitumor potential target. Thus pharmacological inhibitors directed against MNK1 appear to provide an effective and non-harmful anti-tumoral strategy for non-tumour cells. Several studies have shown that the combination of MNKs and mTOR inhibitors increases the antitumor response by inhibiting cell proliferation and inducing apoptosis, relative to the effect obtained with monotherapy. The aim of the project is to obtain a formulation based on a specific aptamer against the kinase MNK1 for application, as monotherapy, combination therapy or replacement therapy, in the treatment of breast cancer. To this end, ApMNKQ2 aptámer, which has already demonstrated antitumor capacity in vitro using breast cancer cell lines, will be conjugated with magnetic nanoparticles (NPM) in order to direct the drug towards the tumor under systemic administration, increasing its effectiveness, protecting against degradation and reducing its toxicity. (English)
12 October 2021
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Madrid
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Identifiers
DTS18_00029
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