The potential role of histone deacetylase inhibitors in the treatment of non-small-cell lung cancer
Abstract
Non-small-cell lung cancer (NSCLC) arises from a complex series of genetic and epigenetic changes leading to uncontrolled cell growth and metastases. The exponential growth in the level of research about the histone deacetylase (HDAC) enzymes, responsible for deacetylating core nucleosomal histones and other proteins, has been driven by the ability of HDAC inhibitors to modulate transcriptional activity. As a result, this therapeutic class is able to block angiogenesis and cell cycling, and promote apoptosis and differentiation. The mechanisms resulting in the antiproliferative biologic effects of these agents are not yet known. Clinical experience indicates these agents generally well tolerated, and active in several haematological and solid tumours. HDAC inhibitors, under clinical evaluation in the treatment of NSCLC patients, are pivanex, CI-994, vorinostat, and LBH589. Here, we discuss about the potential role of HDAC inhibitors focusing on their activity, tolerability, efficacy and future development, in the treatment of NSCLC.
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CI-994 has undergone phase II clinical trials for advanced pancreatic cancer, nonsmall cell lung cancer and multiple myeloma, and phase III clinical trials in combination with gemcitabine for advanced nonsmall-cell lung and pancreatic cancers (discontinued).
“CI-994 has undergone phase II clinical trials for advanced pancreatic cancer, nonsmall cell lung cancer and multiple myeloma [18–20], and has been in phase III clinical trials in combination with gemcitabine for advanced nonsmall-cell lung and pancreatic cancers, though this trial was discontinued [20].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [19]
CI-994 is well tolerated and has undergone phase II/III clinical trials for several types of cancer.
“Importantly, CI-994 is well tolerated and has undergone phase II/III clinical trials for several types of cancer [18–20].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [19]
CI-994 is well tolerated.
“CI-994 is well tolerated and has undergone phase II/III clinical trials for several types of cancer [18–20].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [19]
CI-994 has undergone phase II/III clinical trials for several types of cancer.
“CI-994 is well tolerated and has undergone phase II/III clinical trials for several types of cancer [18–20].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [19]
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Role of Epigenetics in Inflammation-Associated diseases
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The role of protein acetylation in carcinogenesis and targeted drug discovery
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- Authors
- Gridelli, C., Rossi, A., & Maione, P.
- Affiliations
- Azienda Ospedaliera S.Giuseppe Moscati (IT)
- Corresponding author
- Gridelli, Cesare
- ORCID
- Gridelli, Cesare
- Venue
- Critical Reviews in Oncology/Hematology
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 68
- Issue
- 1
- Pages
- 29-36
- ISSN
- 1040-8428 (ISSN-L)
- OpenAlex
- W2068565525
- Cited by
- 54
- References
- 3
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2020: 1 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 6 · 2012: 9
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Critical Reviews in Oncology/Hematology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- histone deacetylase inhibitors, non-small cell lung cancer, vorinostat, panobinostat, CI-994, epigenetic therapy, angiogenesis inhibition, apoptosis, cell cycle arrest, drug tolerability, antiproliferative activity
- MeSH terms
- Vorinostat, Panobinostat, Animals, Antineoplastic Agents, Benzamides, Butyrates, Carcinoma, Non-Small-Cell Lung, Enzyme Inhibitors, Histone Deacetylases, Humans, Hydroxamic Acids, Indoles, Lung Neoplasms, Phenylenediamines, Gene Expression Regulation, Neoplastic, Histone Deacetylase Inhibitors
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