Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
Xiangya School of Medicine, Central South University, Changsha, 410011, Hunan, China.
J Hematol Oncol. 2022 Oct 8;15(1):140. doi: 10.1186/s13045-022-01365-6.
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.
儿科癌症是儿童和青少年死亡的主要原因。由于安全性要求和考虑因素，儿科癌症的治疗策略和药物迄今研究甚少。众所周知，肿瘤细胞往往逐渐逃避细胞死亡途径，这被称为凋亡抵抗，是癌症的标志之一，主导肿瘤耐药性。最近，针对非细胞凋亡性细胞死亡的治疗方法引起了广泛关注。细胞焦亡是一种新的细胞死亡形式，在炎症反应、细胞发育、组织稳态和应激反应中起着重要的生理调节作用。不同形式的细胞焦亡在儿科癌症的治疗中有重要作用。如果采用局部或全身治疗，细胞焦亡可以被诱导，并因此调节肿瘤发生、进展和转移。然而，过度或不受控制的细胞死亡可能导致组织损伤、急性炎症，甚至细胞因子释放综合征，从而促进肿瘤的进展或复发。在此，我们旨在描述细胞焦亡的分子机制，强调和讨论通过多种肿瘤治疗方法在多种儿科肿瘤中激活细胞焦亡途径的挑战和机遇，包括骨肉瘤、神经母细胞瘤、白血病、淋巴瘤和脑肿瘤。
