4.0 Article

Is the focus moving toward a combination of targeted drugs?

Journal

BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
Volume 21, Issue 4, Pages 629-637

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.beha.2008.08.003

Keywords

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

Categories

Funding

  1. NCI NIH HHS [R01 CA093738, R21 CA110953, P50 CA130805, R01 CA100866, RC2 CA148431, R21 CA137823, P50 CA142509] Funding Source: Medline

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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.

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