Senescence modulation reduces tumourigenesis in mouse models of paediatric craniopharyngioma

Abstract

Adamantinomatous craniopharyngiomas (ACP) are histologically benign but clinically aggressive epithelial tumours due to their tendency to invade the brain and relapse. Our group has generated two unique mouse models of ACP and shown that oncogenic b-catenin leads to senescence induction in SOX2+ stem cells with the activation of a robust senescence-associated secretory phenotype (SASP), which is capable of inducing tumours in a paracrine manner. Combining molecular approaches with ex vivo explant cultures and genetic mouse models, we are dissecting the molecular mechanisms underlying this paracrine tumourigenesis. We will present preliminary results using two new mouse models that can ablate senescent cells and modulate the inflammatory arm of the SASP. Our data support a critical role of senescent cells in promoting tumourigenesis in mouse and human ACP and suggest that senolytics and SASP modulators could provide new therapies against these aggressive childhood tumours.