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HDACIs and TKIs combinations and their liposomal delivery for cancer treatment

Cindy Schelker1, Patrycja Nowak-Sliwinska2, Gerrit Borchard2

  • 1School of Pharmaceutical Sciences, Faculty of Sciences, University of Geneva, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland; Translational Research Center in Oncohaematology, Geneva, Switzerland.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|April 10, 2023
PubMed

Insights

Optimizing cancer treatment involves combining Tyrosine Kinase Inhibitors (TKIs) and Histone Deacetylase Inhibitors (HDACIs). Nanocarrier systems enhance the efficacy and safety of these fixed-drug combinations for improved patient outcomes.

Area of Science:

  • Oncology
  • Pharmacology
  • Nanotechnology

Background:

  • Current cancer therapies often lead to drug resistance and toxicity.
  • Fixed-drug combinations are explored to overcome these limitations, but drug-drug interactions and pharmacokinetic profiles require careful management.
  • Tyrosine Kinase Inhibitors (TKIs) and Histone Deacetylase Inhibitors (HDACIs) are key drug classes investigated for combined use.

Purpose of the Study:

  • To review strategies for delivering synergistic drug combinations in cancer treatment.
  • To highlight the role of nanocarrier systems in optimizing fixed-drug combinations.
  • To discuss the safety, tolerability, and efficacy of combined TKI and HDACI therapies.

Main Methods:

  • Review of existing clinical trials and in vivo studies on drug combinations.
  • Analysis of nanocarrier systems, specifically liposomal carriers, for co-loading drugs.
  • Investigation of pharmacokinetic profiles and their impact on synergistic effects.

Main Results:

  • TKIs and HDACIs show safety and tolerability in clinical trials when used separately or in combination.
  • Co-loading TKIs or HDACIs with other anticancer agents in liposomal carriers demonstrates promising in vivo efficacy and safety.
  • Nanocarrier systems can improve the specificity and activity of drug combinations, mitigating pharmacokinetic challenges.

Conclusions:

  • Optimized drug delivery systems, like nanocarriers, are crucial for maximizing the benefits of synergistic drug combinations.
  • Combined TKI and HDACI therapies, when appropriately delivered, offer a promising avenue for enhanced cancer treatment.
  • Further research into nanocarrier-based fixed-drug combinations is warranted to improve cancer therapeutic strategies.
Keywords:
ChemotherapyDrug combinationDrug deliveryDrug-drug interactionHistone deacetylase inhibitorsLiposomesTyrosine kinase inhibitors

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