Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia.
Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia.
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DOI：
10.3390/cancers13184646
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发表时间：
2021-09-16
期刊：
影响因子：
5.2
通讯作者：
Roloff GW
中科院分区：
文献类型：
--
作者：
Ahmadmehrabi K;Haque AR;Aleem A;Griffiths EA;Roloff GW
急性髓细胞白血病（AML）是一种主要的致命性血液癌症。在四十年的时间里，AML的治疗选择仍然相对停滞。最近，多个新的代理商被批准。在这篇综述中，我们讨论了使用这些新批准的疗法的考虑因素。我们概述了AML疾病状态的分子特征，并根据现有数据强调了最适合治疗的患者子集。尽管近几十年来我们对急性髓细胞白血病（AML）的异质性生物学和发病机制的理解有了相当大的增长，但近四十年来，在新疗法领域几乎没有取得进展。然而，自2017年以来，FDA已批准9种药物用于AML患者的前期和复发/难治性（R/R）治疗。这些化合物中的大多数用作关键细胞周期酶途径的抑制剂或白血病增殖和存活的介体。它们已被批准作为单药和与常规或强度降低的常规化疗药物联合使用。在这篇文章中，我们回顾了从头与R/R AML的分子景观，并强调了定义的分子疾病子集的潜在翻译影响。我们还重点介绍了几种最近进入治疗设备的药物，以及它们在AML治疗领域的应用，重点是FLT 3抑制剂，IDH 1和IDH 2抑制剂以及venetoclax。最后，我们结束了调查的两个有前途的新的代理商正在调查，准备进入主流临床竞技场在不久的将来。
Acute myeloid leukemia (AML) is a predominately fatal blood cancer. For a period of forty years, treatment options for AML remained relatively stagnant. Recently, multiple new agents have been approved. In this review, we discuss considerations surrounding the use of these newly approved therapies. We outline the molecular profiles of AML disease status and highlight subsets of patients for whom therapies are best suited based on available data. Despite considerable growth in our understanding of the heterogeneous biology and pathogenesis of acute myeloid leukemia (AML) in recent decades, for nearly forty years, little progress was gained in the realm of novel therapeutics. Since 2017, however, nine agents have been FDA-approved for patients with AML in both the upfront and relapsed/refractory (R/R) settings. Most of these compounds function as inhibitors of key cell cycle enzymatic pathways or mediators of leukemic proliferation and survival. They have been approved both as single agents and in combination with conventional or reduced-intensity conventional chemotherapeutics. In this article, we review the molecular landscape of de novo vs. R/R AML and highlight the potential translational impact of defined molecular disease subsets. We also highlight several recent agents that have entered the therapeutic armamentarium and where they fit in the AML treatment landscape, with a focus on FLT3 inhibitors, IDH1 and IDH2 inhibitors, and venetoclax. Finally, we close with a survey of two promising novel agents under investigation that are poised to enter the mainstream clinical arena in the near future.
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DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
在健康个体中预测急性髓样白血病的风险。
影响因子：
64.8
作者：
Abelson S;Collord G;Ng SWK;Weissbrod O;Mendelson Cohen N;Niemeyer E;Barda N;Zuzarte PC;Heisler L;Sundaravadanam Y;Luben R;Hayat S;Wang TT;Zhao Z;Cirlan I;Pugh TJ;Soave D;Ng K;Latimer C;Hardy C;Raine K;Jones D;Hoult D;Britten A;McPherson JD;Johansson M;Mbabaali F;Eagles J;Miller JK;Pasternack D;Timms L;Krzyzanowski P;Awadalla P;Costa R;Segal E;Bratman SV;Beer P;Behjati S;Martincorena I;Wang JCY;Bowles KM;Quirós JR;Karakatsani A;La Vecchia C;Trichopoulou A;Salamanca-Fernández E;Huerta JM;Barricarte A;Travis RC;Tumino R;Masala G;Boeing H;Panico S;Kaaks R;Krämer A;Sieri S;Riboli E;Vineis P;Foll M;McKay J;Polidoro S;Sala N;Khaw KT;Vermeulen R;Campbell PJ;Papaemmanuil E;Minden MD;Tanay A;Balicer RD;Wareham NJ;Gerstung M;Dick JE;Brennan P;Vassiliou GS;Shlush LI
通讯作者：
Shlush LI
影响因子：
20.3
作者：
Ho, Tzu-Chieh;LaMere, Mark;Becker, Michael W.
通讯作者：
Becker, Michael W.
影响因子：
158.5
作者：
DiNardo, C. D.;Stein, E. M.;Kantarjian, H. M.
通讯作者：
Kantarjian, H. M.
影响因子：
3.7
作者：
Ferrell PB Jr;Diggins KE;Polikowsky HG;Mohan SR;Seegmiller AC;Irish JM
通讯作者：
Irish JM