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GIST Support International - Panobinostat
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Panobinostat (LBH-589) is a highly potent hydroxamic acid–derived deacetylase inhibitor shown to impede multiple pathways implicated in cancer, including cell division, hypoxia response, and angiogenesis . It is sometimes given intravenously, but oral formulations are also being tested.

Manufacturer: Novartis Oncology

Information at manufacturer website: link here 

Definition from NCI Drug Dictionary: Panobinostat (LBH589) is a cinnamic hydroxamic acid analogue with potential antineoplastic activity. Panobinostat selectively inhibits histone deacetylase (HDAC), inducing hyperacetylation of core histone proteins, which may result in modulation of cell cycle protein expression, cell cycle arrest in the G2/M phase and apoptosis. In addition, this agent appears to modulate the expression of angiogenesis-related genes, such as hypoxia-inducible factor-1alpha (HIF-1a) and vascular endothelial growth factor (VEGF), thus impairing endothelial cell chemotaxis and invasion. HDAC is an enzyme that deacetylates chromatin histone proteins.

Available Publications:

Mühlenberg T, Zhang Y, Wagner AJ, Grabellus F, Bradner J, Taeger G, Lang H, Taguchi T, Schuler M, Fletcher JA, Bauer S.
Inhibitors of deacetylases suppress oncogenic KIT signaling, acetylate HSP90, and induce apoptosis in
gastrointestinal stromal tumors
Cancer Res. 2009 Sep 1;69(17):6941-50. 
PubMed PMID: 19706776

Floris G, Debiec-Rychter M, Sciot R, Stefan C, Fieuws S, Machiels K, Atadja P,
Wozniak A, Faa G, Schöffski P.
High efficacy of panobinostat towards human gastrointestinal stromal tumors in a xenograft mouse model. Clin Cancer Res. 2009 Jun 15;15(12):4066-76. 
PubMed PMID: 19509176.

Ellis L, Bots M, Lindemann RK, Bolden JE, Newbold A, Cluse LA, Scott CL, Strasser A, Atadja P, Lowe SW, Johnstone RW.
The histone deacetylase inhibitors LAQ824 and LBH589 do not require death receptor signaling or a functional apoptosome to mediate tumor cell death or therapeutic efficacy.
Blood. 2009 Jul 9;114(2):380-93. PubMed PMID: 19383971.

Marks PA, Xu WS.
Histone deacetylase inhibitors: Potential in cancer therapy.
J Cell Biochem. 2009 Jul 1;107(4):600-8. Review.
PubMed PMID: 19459166; PubMed Central PMCID: PMC2766855.  free access

Prince HM, Bishton MJ, Johnstone RW.
Panobinostat (LBH589): a potent pan-deacetylase inhibitor with promising activity against hematologic and solid tumors.
Future Oncol. 2009 Jun;5(5):601-12. Review.
PubMed PMID: 19519200.

Current Clinical Trials relevant to GIST:

NCT00739414 Dose-escalating Study of LBH589 in Adult Patients With Advanced Solid Tumors

NCT01007968 Pharmacokinetics and Safety of Panobinostat in Patients With Advanced Solid Tumors and Various Degrees of Hepatic Function. Not yet recruiting .

NCT00997399 Study to Evaluate Panobinostat (DACi) Pharmacokinetics and Safety in Solid Tumors and Varying Renal Function.  Not yet recruiting

A Phase I trial using a combination of imatinib plus panobinostat is expected to begin recruiting in Germany in December 2009, with Sebastian Bauer MD as the principal investigator.

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