Combination therapy for cancer: Phototherapy and HDAC inhibition

Jane Jisun Sung, Tom C. Karagiannis

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Otherpeer-review

1 Citation (Scopus)

Abstract

Cutaneous T-cell lymphomas (CTCLs) are rare extranodal non-Hodgkin's characterised by pleomorphic skin lesions and distinct T-cell markers. The annual incidence of these non-Hodgkin's lymphomas are approximately 0.2-0.8/100,000 and mycosis fungoides (MF) or its leukemic variant, Sézary syndrome (SS), account for the majority of cases. CTCL is a relatively benign disease in its early stages, but survival rates decrease significantly as it progresses. As curative therapy remains elusive, the goal of therapy is preventing or slowing progression from early stages while minimising long-term toxicity associated with the treatments. Early-stage CTCL can often be controlled with skin-directed therapies including topical steroids, topical retinoids and phototherapy, while patients with late-stage or refractory MF and SS are given systemic therapies including extracorporeal photopheresis (ECP), interferon (IFN), histone deacetylase inhibitors (HDACi) and denileukin diftitox. Since no single therapy can control disease progression fully, combination therapy is employed to enhance response rates. A novel combination treatment using ultraviolet light phototherapy and HDACi has shown to be a potent radiosensitiser, allowing the use of lower radiation doses and minimising the adverse effects of phototherapy. Such combination reduces the carcinogenic risks associated with the long-term use of phototherapy. Studies have shown that HDACi, such as suberoylanilide hydroxamic acid (Vorinostat, Zolinza®), Romidepsin (Istodax®) and sodium butyrate, induce increased radiosensitivity and decreased double-strand break repair capacity. This is due to the action of HDACi modifying the chromatin compaction and thus changing DNA accessibility. By blocking deacetylation of histones, they promote an open chromatin structure altering the expression of genes involved in cell survival, proliferation, differentiation and apoptosis. As a result, there is a significant increase in the level of ultraviolet-induced apoptosis.

Original languageEnglish
Title of host publicationMolecular Mechanisms and Physiology of Disease
Subtitle of host publicationImplications for Epigenetics and Health
EditorsNilanjana  Maulik, Tom  Karagiannis
Place of PublicationNew York
PublisherSpringer
Pages445-470
Number of pages26
ISBN (Electronic)9781493907069
ISBN (Print)9781493907052
DOIs
Publication statusPublished - 1 Feb 2014
Externally publishedYes

Keywords

  • Cutaneous T-cell lymphoma
  • Histone deacetylase inhibitors
  • Histone deacetylases
  • Iodinated DNA ligand
  • Photochemotherapy
  • Phototherapy
  • Vorinostat

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