Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. High-grade gliomas are primary brain tumors that are incredibly refractory long-term to surgery and chemoradiation, with no proven durable salvage therapies for patients that have failed conventional treatments.
Post-treatment, the latent glioma and its microenvironment are characterized by a senescent-like state of mitotic arrest and a senescence-associated secretory phenotype SASP induced by prior chemoradiation. Although senescence was once thought to be irreversible, recent evidence has demonstrated that cells may escape this state and re-enter the cell cycle, contributing to tumor recurrence.
Moreover, senescent tumor cells could spur the growth of their non-senescent counterparts, thereby accelerating recurrence. In this review, we highlight emerging evidence supporting the use of senolytic agents to ablate latent, senescent-like cells that could contribute to tumor recurrence. We also discuss how senescent cell clearance can decrease the SASP within the tumor microenvironment thereby reducing tumor aggressiveness at recurrence. Finally, senolytics could improve the long-term sequelae of prior therapy on cognition and bone marrow function.
We critically review the senolytic drugs currently under preclinical and clinical investigation and the potential challenges that may be associated with deploying senolytics against latent glioma. In conclusion, senescence in glioma and the microenvironment are critical and potential targets for delaying or preventing tumor recurrence and improving patient functional outcomes through senotherapeutics.
Despite maximal safe surgical resection and aggressive radiation and temozolomide TMZ , all gliomas inevitably recur, typically within the prior treatment field, and often more aggressively than the original tumor 2. Since surgery is typically only performed in the context of newly diagnosed or recurrent disease, relatively little is known about the molecular characteristics and potential drug sensitivity of the latent human glioma cells that contribute to recurrence 3.
