Is the focus moving toward a combination of targeted drugs?

被引：19

作者：

Grant, Steven ^{[1
]}

机构：

[1] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA

来源：

BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY | 2008年 / 21卷 / 04期

关键词：

targeted agents; histone deacetylase inhibitors; HDAC; NF-kappa B inhibitors; CDK inhibitors; proteasome inhibitors; MEK inhibitors; BCL-2; inhibitors;

D O I：

10.1016/j.beha.2008.08.003

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The concept of combining targeted agents for the treatment of acute myeloid leukemia (AML) is a relatively new but potentially promising area of investigation. A number of targeted agents may have limited single-agent activity but Could show significant promise when used in conjunction with other types of similar compounds. Combinations of targeted agents may effectively interrupt multiple pathways in either a linear or parallel fashion. There are currently numerous combination regimens under investigation at either the preclinical or clinical levels, including histone deacetylase (HDAC) and CDK inhibitors; HDAC and proteasome inhibitors; HDAC and NF-kappa B (IKK beta) inhibitors; CHK1 and MEK 1/2 inhibitors; and BCL-2 antagonists and CDK inhibitors. Although combinations of targeted agents will not displace conventional cytotoxic regimens in AML or related disorders in the foreseeable future, these combinations clearly warrant further attention.

引用

收藏

页码：629 / 637

页数：9

相关论文

共 36 条

[1] Subversion of the Bcl-2 life/death switch in cancer development and therapy [J].

Adams, J. M. ;

Huang, D. C. S. ;

Strasser, A. ;

Willis, S. ;

Chen, L. ;

Wei, A. ;

Van Delft, M. ;

Fletcher, J. I. ;

Puthalakath, H. ;

Kuroda, J. ;

Michalak, E. M. ;

Kelly, P. N. ;

Bouillet, P. ;

Villunger, A. ;

O'Reilly, L. ;

Bath, M. L. ;

Smith, D. P. ;

Egle, A. ;

Harris, A. W. ;

Hinds, M. ;

Colman, P. ;

Cory, S. .

Molecular Approaches to Controlling Cancer, 2005, 70 :469-477

[2] Synergistic induction of mitochondrial damage and apoptosis in human leukemia cells by flavopiridol and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) [J].

Almenara, J ;

Rosato, R ;

Grant, S .

LEUKEMIA, 2002, 16 (07) :1331-1343

[3] Chlorambucil cytotoxicity in malignant B lymphocytes is synergistically increased by 2-(morpholin-4-yl)benzo-[h]chomen-4-one (NU7026)-mediated inhibition of DNA double-strand break repair via inhibition of DNA-dependent protein kinase [J].

Amrein, Lilian ;

Loignon, Martin ;

Goulet, Anne-Christine ;

Dunn, Michael ;

Jean-Claude, Bertrand ;

Aloyz, Raquel ;

Panasci, Lawrence .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2007, 321 (03) :848-855

[4] Modeling the initiation and progression of human acute leukemia in mice [J].

Barabe, Frederic ;

Kennedy, James A. ;

Hope, Kristin J. ;

Dick, John E. .

SCIENCE, 2007, 316 (5824) :600-604

[5] Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies [J].

Bhalla, KN .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (17) :3971-3993

[6] Anticancer activities of histone deacetylase inhibitors [J].

Bolden, Jessica E. ;

Peart, Melissa J. ;

Johnstone, Ricky W. .

NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (09) :769-784

[7] Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia [J].

Byrd, John C. ;

Lin, Thomas S. ;

Dalton, James T. ;

Wu, Di ;

Phelps, Mitch A. ;

Fischer, Beth ;

Moran, Mollie ;

Blum, Kristie A. ;

Rovin, Brad ;

Brooker-McEldowney, Michelle ;

Broering, Sarah ;

Schaaf, Larry J. ;

Johnson, Amy J. ;

Lucas, David M. ;

Heerema, Nyla A. ;

Lozanski, Gerard ;

Young, Donn C. ;

Suarez, Jose-Ramon ;

Colevas, A. Dimitrios ;

Grever, Michael R. .

BLOOD, 2007, 109 (02) :399-404

[8] Aggresome induction by proteasome inhibitor bortezomib and α-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells [J].

Catley, Laurence ;

Weisberg, Ellen ;

Kiziltepe, Tanyel ;

Tai, Yu-Tzu ;

Hideshima, Teru ;

Neri, Paola ;

Tassone, Pierfrancesco ;

Atadja, Peter ;

Chauhan, Dharminder ;

Munshi, Nikhil C. ;

Anderson, Kenneth C. .

BLOOD, 2006, 108 (10) :3441-3449

[9] Mcl-1 down-regulation potentiates ABT-737 lethality by cooperatively inducing bak activation and bax translocation [J].

Chen, Shuang ;

Dai, Yun ;

Harada, Hisashi ;

Dent, Paul ;

Grant, Steven .

CANCER RESEARCH, 2007, 67 (02) :782-791

[10] Blockade of histone deacetylase inhibitor-induced RelA/p65 acetylation and NF-κB activation potentiates apoptosis in leukemia cells through a process mediated by oxidative damage, XIAP downregulation, and c-jun n-terminal kinase 1 activation [J].

Dai, Y ;

Rahmani, M ;

Dent, P ;

Grant, S .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (13) :5429-5444

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