Profile of panobinostat and its potential for treatment in solid tumors: an update

被引:57
作者
Anne, Madhurima [1 ]
Sammartino, Daniel [2 ]
Barginear, Myra F. [1 ]
Budman, Daniel [1 ]
机构
[1] Hofstra North Shore LIJ Sch Med, Monter Canc Ctr, Lake Success, NY USA
[2] Hofstra North Shore LIJ Sch Med, Dept Med, Lake Success, NY USA
关键词
panobinostat; LBH589; histone deacetylase inhibitor; solid tumors; HISTONE DEACETYLASE INHIBITOR; HEPATOCELLULAR-CARCINOMA; DAC INHIBITOR; PHASE-I; SUPERIOR EFFICACY; LBH589; INCREASES; OVARIAN-CANCER; LUNG-CANCER; CELL-DEATH; COMBINATION;
D O I
10.2147/OTT.S30773
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
The histone deacetylase (HDAC) inhibitors have emerged as novel therapies for cancer. Panobinostat (LBH 589, Novartis Pharmaceuticals) is a pan-deacetylase inhibitor that is being evaluated in both intravenous and oral formulations across multiple tumor types. Comparable to the other HDACs, panobinostat leads to hyperacetylation of histones and other intracellular proteins, allowing for the expression of otherwise repressed genes, leading to inhibition of cellular proliferation and induction of apoptosis in malignant cells. Panobinostat, analogous to other HDAC inhibitors, also induces apoptosis by directly activating cellular death receptor pathways. Preclinical data suggests that panobinostat has inhibitory activity at nanomolar concentrations and appears to be the most potent clinically available HDAC inhibitor. Here we review the current status of panobinostat and discuss its role in the treatment of solid tumors.
引用
收藏
页码:1613 / 1624
页数:12
相关论文
共 60 条
[1]
Development of the pan-DAC inhibitor panobinostat (LBH589): Successes and challenges [J].
Atadja, Peter .
CANCER LETTERS, 2009, 280 (02) :233-241
[2]
Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90 - A novel basis for antileukemia activity of histone deacetylase inhibitors [J].
Bali, P ;
Pranpat, M ;
Bradner, J ;
Balasis, M ;
Fiskus, W ;
Guo, F ;
Rocha, K ;
Kumaraswamy, S ;
Boyapalle, S ;
Atadja, P ;
Seto, E ;
Bhalla, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (29) :26729-26734
[3]
Bauer S, 2012, J CLIN ONCOL, V30
[4]
Identification of unique synergistic drug combinations associated with downexpression of survivin in a preclinical breast cancer model system [J].
Budman, Daniel R. ;
Calabro, Anthony ;
Rosen, Lisa ;
Lesser, Martin .
ANTI-CANCER DRUGS, 2012, 23 (03) :272-279
[5]
The histone deacetylase inhibitor panobinostat demonstrates marked synergy with conventional chemotherapeutic agents in human ovarian cancer cell lines [J].
Budman, Daniel R. ;
Tai, Julia ;
Calabro, Anthony ;
John, Veena .
INVESTIGATIONAL NEW DRUGS, 2011, 29 (06) :1224-1229
[6]
Histone Deacetylase Inhibition Modulates E-Cadherin Expression and Suppresses Migration and Invasion of Anaplastic Thyroid Cancer Cells [J].
Catalano, Maria Graziella ;
Fortunati, Nicoletta ;
Pugliese, Mariateresa ;
Marano, Francesca ;
Ortoleva, Loredana ;
Poli, Roberta ;
Asioli, Sofia ;
Bandino, Andrea ;
Palestini, Nicola ;
Grange, Cristina ;
Bussolati, Benedetta ;
Boccuzzi, Giuseppe .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, 97 (07) :E1150-E1159
[7]
Cytotoxic activity of the histone deacetylase inhibitor panobinostat (LBH589) in anaplastic thyroid cancer in vitro and in vivo [J].
Catalano, Maria Graziella ;
Pugliese, Mariateresa ;
Gargantini, Eleonora ;
Grange, Cristina ;
Bussolati, Benedetta ;
Asioli, Sofia ;
Bosco, Ornella ;
Poli, Roberta ;
Compagnone, Alessandra ;
Bandino, Andrea ;
Mainini, Franco ;
Fortunati, Nicoletta ;
Boccuzzi, Giuseppe .
INTERNATIONAL JOURNAL OF CANCER, 2012, 130 (03) :694-704
[8]
Low dose histone deacetylase inhibitor, LBH589, potentiates anticancer effect of docetaxel in epithelial ovarian cancer via PI3K/Akt pathway in vitro [J].
Chao, Hongtu ;
Wang, Li ;
Hao, Jingli ;
Ni, Jie ;
Chang, Lei ;
Graham, Peter H. ;
Kearsley, John H. ;
Li, Yong .
CANCER LETTERS, 2013, 329 (01) :17-26
[9]
Characterizing the disposition, metabolism, and excretion of an orally active pan-deacetylase inhibitor, panobinostat, via trace radiolabeled 14C material in advanced cancer patients [J].
Clive, Sally ;
Woo, Margaret M. ;
Nydam, Thomas ;
Kelly, Lindsay ;
Squier, Margaret ;
Kagan, Mark .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2012, 70 (04) :513-522
[10]
Conte P, 2009, J CLIN ONCOL, V27