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Clinical efficiency of epigenetic drugs therapy in bone malignancies

Filomena de Nigris1, Carlo Ruosi2, Claudio Napoli3

  • 1Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.

Bone
|August 24, 2020
PubMed

Insights

Novel epigenetic drugs show promise for bone cancer patients resistant to initial treatments. Combining these agents with other therapies may improve cure rates for these challenging malignancies.

Area of Science:

  • Oncology
  • Epigenetics
  • Pharmacology

Background:

  • Bone malignancies often exhibit poor response to first-line therapies, necessitating novel treatment strategies.
  • Epigenetic modifications play a crucial role in cancer development and progression.
  • Epigenetic drugs offer a promising avenue for overcoming therapeutic resistance in bone cancers.

Purpose of the Study:

  • To provide a comprehensive review of epigenetic agents and their potential in treating bone malignancies.
  • To explore the combination of epigenetic inhibitors with targeted therapies or immune checkpoint blockade.
  • To discuss the optimization of dosing and regimens for enhanced clinical efficacy.

Main Methods:

  • Review of preclinical studies and clinical trials involving epigenetic drugs.
  • Identification of key epigenetic targets, including DNA methyltransferase (DNMT), histone deacetylase (HDAC), lysine-specific histone demethylase (LSD1), isocitrate dehydrogenases, and enhancer of zeste homolog 2 (EZH2).
  • Analysis of combination strategies with targeted therapy and immune checkpoint inhibitors.

Main Results:

  • Several epigenetic drugs, such as Decitabine (DNMTI), Entinostat/Belinostat (HDACI), Olutasidenib (LSD1 inhibitor), and Tazemetostat (EZH2 inhibitor), have shown potential in preclinical settings.
  • Phase II trials predominantly explore combinations of epigenetic inhibitors with targeted therapy or immune checkpoint blockade to enhance therapeutic effects.
  • Optimization of drug dosing and treatment regimens is crucial for improving clinical outcomes.

Conclusions:

  • Epigenetic drugs represent a significant advancement in the treatment of bone malignancies with poor treatment responses.
  • Combination therapies involving epigenetic agents hold promise for improving cure rates in patients with devastating bone cancers.
  • Further optimization of clinical trial designs, including dosing and regimens, is essential for maximizing the efficacy of these novel therapeutic approaches.
Keywords:
BisphosphonatesEpigenetic drugsEwing sarcomaHDACs inhibitorsImmunotherapyOsteosarcoma

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