Topical Formulation of Histone Deacetylase (HDAC) Inhibitors: Treatments for Cancer and Immunological Skin Disorders
Posted Jul 11 2010 5:00pm
Description of Invention: This technology relates to topical formulations of Histone Deacetylase (HDAC) inhibitors (HDIs) that can be used to treat cancers such as cutaneous T-cell lymphoma (CTCL) and skin disorders such as lupus, contact dermatitis, and drug eruptions which are associated with malignant or autoreactive lymphocytes from the immune system. HDIs, such as depsipeptide, have been demonstrated to be effective against CTCL when administered internally but a topical preparation may be more useful for treatment at earlier stages of the disease.
HDIs are molecules that inhibit the activity of a group of enzymes that remove small chemical groups called acetyl groups from many different proteins, including proteins that regulate gene expression. By altering the acetylation of these proteins, HDAC inhibitors can induce tumor cell differentiation, cell cycle arrest, and cell death. A variety of chemically distinct molecules exhibit HDAC inhibitory activity and their potential as therapeutics for cancer and other indications is being investigated. The HDI depsipeptide is a cyclical peptide derived from a bacterium and is indicated as a second line treatment for CTCL through intravenous administration. Development of a topical preparation of depsipeptide and/or other HDAC inhibitors may help reduce their toxicity and increase their effectiveness in treating CTCL, other cancers, as well as other diseases.
Use as a topical therapeutic for treatment of skin lymphomas
Use as a topical therapeutic for treatment of immunological skin disorders
HDIs such as vorinostat and depsipeptide have received regulatory approval for clinical use in systemic treatment of CTCL.
Localized topical treatment reduces potential for adverse reactions compared to systemic treatments.
Clinical data illustrating the effectiveness of the topical formulation of depsipeptide are available.
Development Status: In early stage of clinical development
Piekarz RL et al. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol. 2009 Nov 10;27(32):5410-5417. [ PubMed: 19826128 ]
Licensing Status: Available for licensing.
Collaborative Research Opportunity: The Center for Cancer Research, Medical Oncology Branch and Affiliates, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize topical therapy using HDIs. Please contact John Hewes, Ph.D. at 301-435-3121 or firstname.lastname@example.org for more information. Click here to view the NCI collaborative opportunity announcement.