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目前ATRT的分子和临床景观 - 与未来疗法的联系

Katharina Gastberger^1,2, Victoria E Fincke^1,2, Marlena Mucha^1,2

¹Pediatrics and Adolescent Medicine, Swabian Children's Cancer Center, University Medical Center Augsburg, Augsburg, Germany.

Cancer management and research

|December 13, 2023

概括

非典型的形形形瘤 (ATRT) 是一种侵袭性的儿科脑癌. 需要针对瘤异质性的新型组合疗法,因为单个药物的复发率高,成功率有限.

科学领域:

儿科瘤学儿科瘤学
神经瘤学神经瘤学
癌症遗传学癌症遗传学

背景情况:

非典型的甲状腺形形瘤 (ATRT) 是一种罕见的,侵袭性的儿科中枢神经系统 (CNS) 癌症.
遗传特征包括SMARCB1/INI1或SMARCA4/BRG1无活化,一些病例与形瘤倾向综合征 (RTPS) 相关.
独特的DNA甲基化亚型 (ATRT-MYC, -TYR, -SHH) 和临床因素影响预后.

研究的目的:

批判性地评估ATRT当前的多式模式治疗方案.
评估新兴的向治疗方法及其在临床试验中的潜力.
突出需要新的策略来解决初级和复发性/耐药性ATRT的高复发率.

主要方法:

审查目前的传统多式疗法方案,包括放射治疗 (RT) 和高剂量化疗 (HDCT).
评估新兴的向治疗方法,如免疫检查点抑制剂和表观遗传活性剂.
对影响生存的临床风险因素和DNA甲基化亚型的分析.

主要成果:

传统治疗,包括RT和HDCT,在平衡疗效和毒性方面面临挑战,复发率为40-75%.
向单剂疗法表现出有限的成功,可能是由于ATRT的低突变负担和获得的耐药性.
DNA甲基化亚型影响对特定药物的反应,强调了生物异质性.

结论:

基于机制的组合疗法被假设在ATRT中增强治疗反应.
未来的ATRT治疗应该包含风险组调整的协议,尊重临床和生物异质性.
个性化治疗策略对于改善这一具有挑战性的儿科恶性瘤的结果至关重要.

关键词:

这就是为什么我们会这样做.在CNS中,CNS是CNS.在SMARCB1中,与SWI/SNF相关的矩阵相关联.染色素的行为依赖调节器.非典型的甲状腺形形瘤.细胞循环中的细胞循环.中枢神经系统中枢神经系统成员 1 成员 1 儿科儿科儿科亚家族b 亚家族b 亚家族治疗治疗治疗治疗治疗治疗

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