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Combination Therapies Targeting HDAC and IKK in Solid Tumors.
- Source :
-
Trends in pharmacological sciences [Trends Pharmacol Sci] 2018 Mar; Vol. 39 (3), pp. 295-306. Date of Electronic Publication: 2017 Dec 09. - Publication Year :
- 2018
-
Abstract
- The rationale for developing histone deacetylase (HDAC) inhibitors (HDACi) as anticancer agents was based on their ability to induce apoptosis and cell cycle arrest in cancer cells. However, while HDACi have been remarkably effective in the treatment of hematological malignancies, clinical studies with HDACi as single agents in solid cancers have been disappointing. Recent studies have shown that, in addition to inducing apoptosis in cancer cells, class I HDACi induce IκB kinase (IKK)-dependent expression of proinflammatory chemokines, such as interleukin-8 (IL8; CXCL8), resulting in the increased proliferation of tumor cells, and limiting the effectiveness of HDACi in solid tumors. Here, we discuss the mechanisms responsible for HDACi-induced CXCL8 expression, and opportunities for combination therapies targeting HDACs and IKK in solid tumors.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents administration & dosage
Antineoplastic Agents pharmacology
Antineoplastic Combined Chemotherapy Protocols
Apoptosis drug effects
Histone Deacetylase Inhibitors administration & dosage
Histone Deacetylase Inhibitors pharmacology
Humans
I-kappa B Kinase metabolism
Interleukin-8 metabolism
Neoplasms metabolism
Protein Kinase Inhibitors administration & dosage
Protein Kinase Inhibitors pharmacology
Antineoplastic Agents therapeutic use
Histone Deacetylase Inhibitors therapeutic use
I-kappa B Kinase antagonists & inhibitors
Neoplasms drug therapy
Protein Kinase Inhibitors therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3735
- Volume :
- 39
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Trends in pharmacological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 29233541
- Full Text :
- https://doi.org/10.1016/j.tips.2017.11.008