Acceleration or Brakes: Which Is Rational for Cell Cycle-Targeting Neuroblastoma Therapy?
Acceleration or Brakes: Which Is Rational for Cell Cycle-Targeting Neuroblastoma Therapy?
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DOI：
10.3390/biom11050750
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发表时间：
2021-05-18
期刊：
影响因子：
5.5
通讯作者：
Nakagawara A
中科院分区：
文献类型：
--
作者：
Ando K;Nakagawara A
无节制的增殖是恶性肿瘤的共同特征。以细胞周期为靶点是防止细胞无限分裂的治疗策略。最近开发的这些选择性抑制剂的原理可以细分为两类具有相反功能的药物。一种是对细胞周期施加“刹车”，以阻止细胞增殖，例如使用细胞周期酶抑制剂。另一种是“加速”细胞周期，以启动复制/有丝分裂灾难，例如使用细胞周期检查点激酶的抑制剂。细胞周期进展或停滞的命运分别受到可耐受或过度DNA损伤的存在的严格控制。这表明DNA修复激酶的抑制剂，如PARP抑制剂和细胞周期检查点激酶的抑制剂之间存在配伍关系。在目前的综述中，我们探讨了在不利的神经母细胞瘤中伴随着DNA损伤修复机制改变的细胞周期的变化，这与它们独特的基因组和分子特征有关。我们强调了这些更改的漏洞，这些漏洞可归因于每个更改的功能。在评估的基础上，我们为个性化药物提供了可能的治疗方法，这些方法似乎是对立的，但两者都是针对不利的神经母细胞瘤细胞周期改变的有希望的策略。
Unrestrained proliferation is a common feature of malignant neoplasms. Targeting the cell cycle is a therapeutic strategy to prevent unlimited cell division. Recently developed rationales for these selective inhibitors can be subdivided into two categories with antithetical functionality. One applies a “brake” to the cell cycle to halt cell proliferation, such as with inhibitors of cell cycle kinases. The other “accelerates” the cell cycle to initiate replication/mitotic catastrophe, such as with inhibitors of cell cycle checkpoint kinases. The fate of cell cycle progression or arrest is tightly regulated by the presence of tolerable or excessive DNA damage, respectively. This suggests that there is compatibility between inhibitors of DNA repair kinases, such as PARP inhibitors, and inhibitors of cell cycle checkpoint kinases. In the present review, we explore alterations to the cell cycle that are concomitant with altered DNA damage repair machinery in unfavorable neuroblastomas, with respect to their unique genomic and molecular features. We highlight the vulnerabilities of these alterations that are attributable to the features of each. Based on the assessment, we offer possible therapeutic approaches for personalized medicine, which are seemingly antithetical, but both are promising strategies for targeting the altered cell cycle in unfavorable neuroblastomas.
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复发的神经母细胞瘤显示出频繁的RAS-MAPK途径突变。
影响因子：
30.8
作者：
Eleveld TF;Oldridge DA;Bernard V;Koster J;Colmet Daage L;Diskin SJ;Schild L;Bentahar NB;Bellini A;Chicard M;Lapouble E;Combaret V;Legoix-Né P;Michon J;Pugh TJ;Hart LS;Rader J;Attiyeh EF;Wei JS;Zhang S;Naranjo A;Gastier-Foster JM;Hogarty MD;Asgharzadeh S;Smith MA;Guidry Auvil JM;Watkins TB;Zwijnenburg DA;Ebus ME;van Sluis P;Hakkert A;van Wezel E;van der Schoot CE;Westerhout EM;Schulte JH;Tytgat GA;Dolman ME;Janoueix-Lerosey I;Gerhard DS;Caron HN;Delattre O;Khan J;Versteeg R;Schleiermacher G;Molenaar JJ;Maris JM
通讯作者：
Maris JM
DOI：
10.1126/science.aat6768
发表时间：
2018-12-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ackermann S;Cartolano M;Hero B;Welte A;Kahlert Y;Roderwieser A;Bartenhagen C;Walter E;Gecht J;Kerschke L;Volland R;Menon R;Heuckmann JM;Gartlgruber M;Hartlieb S;Henrich KO;Okonechnikov K;Altmüller J;Nürnberg P;Lefever S;de Wilde B;Sand F;Ikram F;Rosswog C;Fischer J;Theissen J;Hertwig F;Singhi AD;Simon T;Vogel W;Perner S;Krug B;Schmidt M;Rahmann S;Achter V;Lang U;Vokuhl C;Ortmann M;Büttner R;Eggert A;Speleman F;O'Sullivan RJ;Thomas RK;Berthold F;Vandesompele J;Schramm A;Westermann F;Schulte JH;Peifer M;Fischer M
通讯作者：
Fischer M
影响因子：
64.8
作者：
Bartkova, Jirina;Rezaei, Nousin;Gorgoulis, Vassilis G.
通讯作者：
Gorgoulis, Vassilis G.
影响因子：
64.8
作者：
Di Micco, Raffaella;Fumagalli, Marzia;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
影响因子：
64.5
作者：
Buis J;Wu Y;Deng Y;Leddon J;Westfield G;Eckersdorff M;Sekiguchi JM;Chang S;Ferguson DO
通讯作者：
Ferguson DO