Traitement du cancer du sein triple négatif à l’aide de nanothérapies à base d’ARN
DOI :
https://doi.org/10.18192/osurj.v5i2.8056Résumé
Le cancer du sein triple négatif est une forme particulièrement agressive de cancer du sein, qui demeure difficile à traiter. Même s’il ne représente qu’une partie des cas de cancer du sein, il est responsable d’un nombre important de décès liés à cette maladie. Cette difficulté s’explique en partie par l’absence des récepteurs ER, PR et HER2, qui sont normalement utilisés comme cibles dans certains traitements. Comme ces récepteurs sont absents, les options de thérapies ciblées sont limitées, et la chimiothérapie reste souvent le principal traitement utilisé.
Cependant, la chimiothérapie présente plusieurs limites. Elle peut entraîner des effets toxiques importants, et les cellules cancéreuses peuvent rapidement développer une résistance aux médicaments. De plus, même après un traitement, la tumeur peut réapparaître, notamment à cause de la présence de cellules souches cancéreuses. Ces cellules ont la capacité de survivre aux traitements et de contribuer à la rechute de la maladie. Elles peuvent aussi exister sous différents états, notamment un état de type mésenchymateux et un état de type épithélial. Comme ces états peuvent se transformer l’un en l’autre, cibler seulement un type de cellule souche cancéreuse peut permettre à l’autre type de se développer, ce qui favorise la progression ou le retour du cancer.
Cette étude vise donc à développer et à évaluer des nanothérapies à base d’ARN capables de cibler certaines molécules régulatrices impliquées dans la survie du cancer du sein triple négatif et dans le maintien des cellules souches cancéreuses. Plus précisément, le projet examine le rôle d’un microARN particulier ainsi que d’un ARNm ayant des propriétés suppressives contre le cancer. L’objectif est de déterminer si ces molécules peuvent réduire les signaux oncogéniques, c’est-à-dire les signaux qui favorisent le développement du cancer, et diminuer la population de cellules souches cancéreuses. Pour permettre leur entrée efficace dans les cellules cancéreuses, ces ARN sont incorporés dans des nanoparticules, qui sont ensuite préparées et caractérisées.
L’efficacité de ces nanoparticules contenant de l’ARN est évaluée à l’aide de plusieurs méthodes en laboratoire. Les changements dans l’expression des gènes sont mesurés par RT-qPCR. Les niveaux de protéines ainsi que certains marqueurs associés aux cellules souches cancéreuses, comme CD44 et ALDH, sont analysés par cytométrie en flux. La viabilité des cellules tumorales est aussi évaluée à l’aide de tests comme MTT et PrestoBlue, qui permettent de mesurer la survie et l’activité métabolique des cellules.
Dans l’ensemble, on s’attend à ce que ces nanothérapies à base d’ARN réduisent à la fois la viabilité des cellules tumorales du cancer du sein triple négatif et les caractéristiques associées aux cellules souches cancéreuses. Cela pourrait aider à limiter la progression de la tumeur et à réduire le risque de récidive. Ce travail pourrait donc contribuer au développement de traitements plus ciblés contre le cancer du sein triple négatif, en utilisant des approches basées sur l’ARN pour atteindre des cibles souvent considérées comme difficiles à traiter avec les médicaments classiques.
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