Pineoblastoma (PB) is a rare yet lethal pediatric brain cancer of the pineal gland, a small endocrine organ that secretes melatonin to regulate the circadian rhythm. For PB patients ≤5 years of age, the overall survival rate is approximately 15%; metastatic PB is incurable. Standard treatment, including surgical resection, radiation, and systemic chemotherapy, improves survival but compromises neurocognitive function. A better understanding of the disease and the generation of preclinical models may enable re-evaluation of previous clinical trials, development of precision therapeutic strategies and improve patient outcome. Over the past 5 years, PB has been recognized to include several major subtypes driven by (i) loss of microRNA processing factorsDICERandDROSHAcharacterized by a relatively good prognosis; (ii) loss of the retinoblastoma tumor suppressorRB1; and (iii) amplification or induction of thecMYCprotooncogene, with the latter two subtypes exhibiting exceedingly poor prognosis. Recently, mouse models for the major PB subtypes (RB1-,DICER1- andDROSHA-) exceptMYC- have been established. This progress, including better understanding of the disease, cell of origin, tumor progression, role of autophagy, and targetable vulnerabilities, holds promise for novel therapeutic strategies to combat each subtype of this lethal childhood malignancy.
松果体母细胞瘤是一种罕见但致命的儿童脑癌，起源于松果体——一个分泌褪黑素以调节昼夜节律的小型内分泌器官。对于年龄≤5岁的患者，其总体生存率约为15%；而转移性松果体母细胞瘤目前尚无法治愈。标准治疗方案包括手术切除、放疗和全身化疗，虽能提高生存率，但会损害神经认知功能。深入理解该疾病并建立临床前模型，可能有助于重新评估既往临床试验、开发精准治疗策略并改善患者预后。近五年来，研究已确认松果体母细胞瘤包含几个主要亚型，其驱动机制分别为：（1）预后相对较好的微RNA加工因子DICER和DROSHA缺失型；（2）视网膜母细胞瘤抑癌基因RB1缺失型；（3）原癌基因cMYC扩增或诱导型，后两种亚型预后极差。近期，除MYC亚型外，针对主要亚型（RB1缺失型、DICER1缺失型和DROSHA缺失型）的小鼠模型已成功建立。这些进展——包括对疾病本质、起源细胞、肿瘤进展过程、自噬作用及靶向治疗薄弱环节的深入认识——为开发针对各亚型的新型治疗策略提供了希望，有望攻克这种致命的儿童恶性肿瘤。
肿瘤(癌症)患者之家