Using functional genomics to overcome therapeutic resistance in hematological malignancies.
Using functional genomics to overcome therapeutic resistance in hematological malignancies.
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DOI：
10.1007/s12026-012-8353-z
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发表时间：
2013-03
影响因子：
4.4
通讯作者：
DeGregori, James
中科院分区：
文献类型：
--
作者：
Alvarez-Calderon, Francesca;Gregory, Mark A.;DeGregori, James
关键词：
尽管我们对恶性转化相关驱动事件的理解取得了很大进展，但只有少数致癌驱动因素被针对并转化为切实的临床益处。此外，即使靶向治疗能够有效抑制致癌驱动因素，导致癌症缓解，疾病持续存在和/或复发通常也是不可避免的。癌症的复发可能是由于内在或获得性耐药机制导致无法消除所有癌细胞所致。耐药的内在机制包括肿瘤异质性和可以补偿致癌驱动因素抑制的途径。获得性耐药机制包括致癌驱动因素的突变，以直接阻止药物介导的抑制和补偿性生存途径的激活。基于 RNA 干扰 (RNAi) 的筛选为探究内在和获得性耐药机制提供了一种强大的方法。针对所有人类和小鼠基因的短干扰 (si)RNA 文库的可用性使得进行大规模无偏见筛选成为可能，以确定特定基因型的癌细胞或特定治疗后特别需要的途径，从而有助于设计可能限制耐药机制的潜在新治疗策略。在这篇综述中，我们将讨论如何使用 RNAi 筛选来揭示关键的生长和生存途径，并帮助确定新的治疗靶点，以改善血液恶性肿瘤的治疗。
Despite great advances in our understanding of the driving events involved in malignant transformation, only a small number of oncogenic drivers have been targeted and translated into tangible clinical benefit. Moreover, even when a targeted therapy can be shown to effectively inhibit an oncogenic driver, leading to cancer remission, disease persistence and/or relapse is typically inevitable. Reemergence of the cancer can result from either intrinsic or acquired resistance mechanisms that result in failure to eliminate all cancer cells. Intrinsic mechanisms of resistance include tumor heterogeneity and pathways that can compensate for the inhibition of the oncogenic driver. Acquired resistance mechanisms include mutation of the oncogenic driver to directly prevent drug-mediated inhibition and the activation of compensatory survival pathways. RNA interference (RNAi)-based screening provides a powerful approach for the interrogation of both intrinsic and acquired resistance mechanisms. The availability of short interfering (si)RNA libraries targeting all human and mouse genes has made it possible to perform large-scale unbiased screens to identify pathways that are specifically required in cancer cells of particular genotypes or following particular treatments, facilitating the design of potential new therapeutic strategies that may limit resistance mechanisms. In this review, we will discuss how RNAi screens can be used to uncover critical growth and survival pathways and aid in the identification of novel therapeutic targets for improved treatment of hematological malignancies.
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影响因子：
15.9
作者：
Bellodi, Cristian;Lidonnici, Maria Rosa;Calabretta, Bruno
通讯作者：
Calabretta, Bruno
影响因子：
20.3
作者：
Bagrintseva, K;Schwab, R;Spiekermann, K
通讯作者：
Spiekermann, K
DOI：
10.4049/jimmunol.0902443
发表时间：
2010-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Astier AL;Beriou G;Eisenhaure TM;Anderton SM;Hafler DA;Hacohen N
通讯作者：
Hacohen N
影响因子：
20.3
作者：
Bélanger, SD;St-Pierre, Y
通讯作者：
St-Pierre, Y
影响因子：
7.3
作者：
Astsaturov I;Ratushny V;Sukhanova A;Einarson MB;Bagnyukova T;Zhou Y;Devarajan K;Silverman JS;Tikhmyanova N;Skobeleva N;Pecherskaya A;Nasto RE;Sharma C;Jablonski SA;Serebriiskii IG;Weiner LM;Golemis EA
通讯作者：
Golemis EA