Medulloblastoma and the DNA Damage Response.
Medulloblastoma and the DNA Damage Response.
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DOI：
10.3389/fonc.2022.903830
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发表时间：
2022
影响因子：
4.7
通讯作者：
Kenney, Anna Marie
中科院分区：
文献类型：
--
作者：
McSwain, Leon F.;Parwani, Kiran K.;Shahab, Shubin W.;Hambardzumyan, Dolores;MacDonald, Tobey J.;Spangle, Jennifer M.;Kenney, Anna Marie
髓母细胞瘤(MB)是儿童最常见的恶性脑肿瘤，其治疗标准包括手术、放疗和化疗。最近的分子图谱导致了四个分子上不同的MB亚群的识别-Wingless(WNT)，Sonic Hedgehog(SHH)，Group 3和Group 4。尽管MB基因组特征和随后的肿瘤分层，临床治疗模式仍然主要受组织学、手术切除程度和有无转移的驱动，而不是分子图谱。患者通常接受肿瘤切除，然后进行颅脊放射治疗(CSI)，并接受6个月至1年的多药化疗方案。虽然显然有必要开发针对每个患者的分子变化的靶向试剂，但无论分子亚类如何，负责DNA损伤修复的靶向蛋白可能会产生更广泛的影响。DNA损伤反应(DDR)蛋白抑制剂最近已成为靶向药物，作为单一治疗或联合治疗不同癌症具有很强的活性。在这里，我们讨论了MB基因组不稳定性的分子基础，以及通过DNA损伤反应抑制来开发的潜在途径。
Medulloblastoma (MB) is the most common malignant brain tumor in children with standard of care consisting of surgery, radiation, and chemotherapy. Recent molecular profiling led to the identification of four molecularly distinct MB subgroups – Wingless (WNT), Sonic Hedgehog (SHH), Group 3, and Group 4. Despite genomic MB characterization and subsequent tumor stratification, clinical treatment paradigms are still largely driven by histology, degree of surgical resection, and presence or absence of metastasis rather than molecular profile. Patients usually undergo resection of their tumor followed by craniospinal radiation (CSI) and a 6 month to one-year multi-agent chemotherapeutic regimen. While there is clearly a need for development of targeted agents specific to the molecular alterations of each patient, targeting proteins responsible for DNA damage repair could have a broader impact regardless of molecular subgrouping. DNA damage response (DDR) protein inhibitors have recently emerged as targeted agents with potent activity as monotherapy or in combination in different cancers. Here we discuss the molecular underpinnings of genomic instability in MB and potential avenues for exploitation through DNA damage response inhibition.
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影响因子：
2.3
作者：
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通讯作者：
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影响因子：
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