Despite being extensively studied for several decades, the microtubule-associated protein Tau has not finished revealing its secrets. For long, Tau has been known for its ability to promote microtubule assembly. A less known feature of Tau is its capability to bind to cancer-related protein kinases, suggesting a possible role of Tau in modulating microtubule-independent cellular pathways that are associated with oncogenesis. With the intention of finding new therapeutic targets for cancer, it appears essential to examine the interaction of Tau with these kinases and their consequences. This review aims at collecting the literature data supporting the relationship between Tau and cancer with a particular focus on glioblastoma tumors in which the pathological significance of Tau remains largely unexplored. We will first treat this subject from a mechanistic point of view showing the pivotal role of Tau in oncogenic processes. Then, we will discuss the involvement of Tau in dysregulating critical pathways in glioblastoma. Finally, we will outline promising strategies to target Tau protein for the therapy of glioblastoma.

Tau protein has been described for several decades as a promoter of tubulin assembly into microtubules. Dysregulation or alterations in Tau expression have been related to various brain cancers, including the highly aggressive and lethal brain tumor glioblastoma multiform (GBM). In this respect, Tau holds significant promise as a target for the development of novel therapies. Here, we examined the structure–activity relationship of a new series of seventeen 2-aminothiazole-fused to flavonoid hybrid compounds (TZF) on Tau binding, Tau fibrillation, and cellular effects on Tau-expressing cancer cells. By spectrofluorometric approach, we found that two compounds, 2 and 9, demonstrated high affinity for Tau and exhibited a strong propensity to inhibit Tau fibrillation. Then, the biological activity of these compounds was evaluated on several Tau-expressing cells derived from glioblastoma. The two lead compounds displayed a high anti-metabolic activity on cells related to an increased fission of the mitochondria network. Moreover, we showed that both compounds induced microtubule bundling within newly formed neurite-like protrusions, as well as with defection of cell migration. Taken together, our results provide a strong experimental basis to develop new potent molecules targeting Tau-expressing cancer cells, such as GBM.

Silicone breast implants have long been associated with the gradual release of low molecular weight siloxanes from the inner gel through the implant membrane into the periprosthetic biological environment, a phenomenon commonly referred to as “gel bleed.” Despite more than five decades of investigation spanning polymer science, transport theory, and biomedical research, the physicochemical mechanisms underlying silicone permeation remain conceptually fragmented. Here, we revisit silicone permeation by examining how molecular transport arises from the intrinsic interplay between polymer architecture, thermodynamic partitioning, and diffusional mobility within crosslinked networks. We further analyze the key determinants of permeation, including implant aging, barrier‐layer technologies, and interaction with the periprosthetic tissue environment. We further discuss how dynamic bio‐interfaces influence bidirectional transport and bioaccumulation in vivo. Beyond their implications for implant performance, these observations provide broader conceptual insights into mass transport in soft materials, highlighting general principles relevant to elastomers, hydrogels, and drug‐delivery systems. By integrating material structure, transport physics and host interactions, this review establishes a mechanistic viewpoint on polymer permeation in vivo and offers design considerations for next‐generation soft implantable biomaterials.

En dépit d’être extrêmement étudiée depuis plusieurs décennies, la protéine Tau n’a très certainement pas encore révélé tous ses secrets. Son rôle majeur est de favoriser l'assemblage de la tubuline en microtubules. Une dysrégulation ou une altération de son expression sont corrélées à diverses pathologies, y compris les cancers. À cet égard, Tau peut représenter une nouvelle cible prometteuse pour le développement de thérapies innovantes. Dans cette étude, la relation structure-activité d'une nouvelle série de dix-sept composés hybrides thiazoloflavonoïdes (TZF), combinant un hétérocycle flavonoïde fusionné avec le thiazole, a été examiné en termes d’interaction avec Tau, d’effet sur la fibrillation de Tau et d’activité biologique sur les cellules cancéreuses dérivées du glioblastome ainsi que sur des sphéroïdes multicellulaires 3D (MCS) exprimant Tau. Deux TZF, 2 et 9, se caractérisent in vitro par une forte affinité pour Tau associée à une forte inhibition de la fibrillation de la protéine. Au niveau cellulaire, ces TZF montrent une activité anti-métabolique corrélée au niveau d’expression de Tau, et qui est due à une fragmentation du réseau mitochondrial. De plus, uniquement les cellules exprimant Tau présentent des « bundles » de microtubules au sein de protrusions de type neurite nouvellement formées. Chez ces cellules, le remodelage du cytosquelette microtubulaire affecte négativement les paramètres migratoires. Enfin, mes travaux montrent également que le composé 9 induit une inhibition de la croissance des MCS exprimant Tau. Ces résultats révèlent le potentiel prometteur de TZF pour cibler Tau dans les cancers exprimant Tau et dans d’autres pathologies liées à Tau.