Europe PMC
Nothing Special   »   [go: up one dir, main page]

Europe PMC requires Javascript to function effectively.

Either your web browser doesn't support Javascript or it is currently turned off. In the latter case, please turn on Javascript support in your web browser and reload this page.

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

Combination treatment with histone deacetylase and carbonic anhydrase 9 inhibitors shows therapeutic potential in experimental diffuse intrinsic pontine glioma.

Author information

Affiliations

  • 1. Cell Biology Research Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
      Authors
    • Fujita N 1, 2
    • Bondoc A 1
    • Simoes S 1
    • Ishida J 1
    • Taccone MS 1
    • Luck A 1
    • Srikanthan D 1
    • Siddaway R 1
    • Levine A 1
    • Sabha N 1
    • Krumholtz S 1
    • Smith C 1
    • Hawkins C 1
    • Rutka J 1
    (14 authors)
  • 2. Department of Neurosurgery, Juntendo University School of Medicine, Bunkyo-Ku, Tokyo, 113-8421, Japan.
      Authors
    • Fujita N 1, 2
    • Kondo A 2
    • Arai H 2
    (3 authors)
  • 3. Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, BC, V5Z 1L3, Canada.
      Authors
    • McDonald P 3
    • Dedhar S 3
    (2 authors)

ORCIDs linked to this article

Brain Tumor Pathology, 24 Sep 2024, 41(3-4):117-131
https://doi.org/10.1007/s10014-024-00493-w PMID: 39316272 

This article is based on a previously available preprint.

Abstract 

Diffuse intrinsic pontine glioma (DIPG) remains a significant therapeutic challenge due to the lack of effective and safe treatment options. This study explores the potential of combining histone deacetylase (HDAC) and carbonic anhydrase 9 (CA9) inhibitors in treating DIPG. Analysis of RNA sequencing data and tumor tissue from patient samples for the expression of the carbonic anhydrase family and hypoxia signaling pathway activity revealed clinical relevance for targeting CA9 in DIPG. A synergy screen was conducted using CA9 inhibitor SLC-0111 and HDAC inhibitors panobinostat, vorinostat, entinostat, and pyroxamide. The combination of SLC-0111 and pyroxamide demonstrated the highest synergy and was selected for further analysis. Combining SLC-0111 and pyroxamide effectively inhibited DIPG cell proliferation, reduced cell migration and invasion potential, and enhanced histone acetylation, leading to decreased cell population in S Phase. Additionally, the combination therapy induced a greater reduction in intracellular pH than either agent alone. Data from this study suggest that the combination of SLC-0111 and pyroxamide holds promise for treating experimental DIPG, and further investigation of this combination therapy in preclinical models is warranted to evaluate its potential as a viable treatment for DIPG.

Full text links 

Read article at publisher's site: https://doi.org/10.1007/s10014-024-00493-w

References 

Articles referenced by this article (45)

Show 10 more references (10 of 45)

Citations & impact 

This article has not been cited yet.

Impact metrics

1
Data citation
Jump to Data

Data 

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.

Funding 

Funders who supported this work.

CIHR (1)

Canadian Institutes of Health Research (1)

Cure Starts Now Foundation

    Curing Kids Cancer