The emerging role of pyroptosis in pediatric cancers: from mechanism to therapy

Abstract

Pediatric cancers are the driving cause of death for children and adolescents. Due to safety requirements and considerations, treatment strategies and drugs for pediatric cancers have been so far scarcely studied. It is well known that tumor cells tend to progressively evade cell death pathways, which is known as apoptosis resistance, one of the hallmarks of cancer, dominating tumor drug resistance. Recently, treatments targeting nonapoptotic cell death have drawn great attention. Pyroptosis, a newly specialized form of cell death, acts as a critical physiological regulator in inflammatory reaction, cell development, tissue homeostasis and stress response. The action in different forms of pyroptosis is of great significance in the therapy of pediatric cancers. Pyroptosis could be induced and consequently modulate tumorigenesis, progression, and metastasis if treated with local or systemic therapies. However, excessive or uncontrolled cell death might lead to tissue damage, acute inflammation, or even cytokine release syndrome, which facilitates tumor progression or recurrence. Herein, we aimed to describe the molecular mechanisms of pyroptosis, to highlight and discuss the challenges and opportunities for activating pyroptosis pathways through various oncologic therapies in multiple pediatric neoplasms, including osteosarcoma, neuroblastoma, leukemia, lymphoma, and brain tumors.

Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research

“…Cell death (especially cell suicide) plays a fundamental role in maintaining physiological homeostasis by removing damaged cells, and it may also be an aberrant pathological reaction to damaging stimuli [1]. The Nomenclature of Cell Death Committee has developed guidelines to divide cell death modes into accidental cell death and regulated cell death (RCD) according to morphology, biochemistry, and function [2].…”

Therapy resistance in neuroblastoma: Mechanisms and reversal strategies

“…For instance, chemotherapy in combination with miR-based treatment was regarded as a promising method for clinical management of progressive NB. Novel strategies have been proposed and are under investigation such as inducing pyroptosis in apoptosis resistant-NB cells ( Wang et al, 2022 ). In conclusion, this review demonstrated the complex mechanisms ( Figure 2 ) and various reversal strategies ( Figure 3 ; Table 2 ) of NB resistance to multiple treatments.…”

CircDOCK1 Regulates miR-186/DNMT3A to Promote Osteosarcoma Progression

“…In young adults and children, OS is a common osseous malignancy [ 17 , 18 ]. Although the five-year survival was elevated over the last 3 decades for the OS population, their prognosis is still poor, making it necessary to discover new diagnostic and therapeutic targets for the management of OS [ 19 , 20 , 21 ]. The advantages of circRNA, such as its structural stability and tissue specificity, have attracted the attention of researchers in recent years [ 22 , 23 ].…”