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Off-target anti-leukemic effects of antibiotics: mechanisms and therapeutic insights

Jason Charamis1, Nikolaos Katzilakis2, Eftichia Stiakaki2

  • 1Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation, Academy of Athens, Athens, 11527, Greece.

Cancer Chemotherapy and Pharmacology
|July 6, 2026
PubMed

Insights

Antibiotics can harm blood cells, but this toxicity may also reveal leukemia vulnerabilities. Researchers explored this link, finding potential therapeutic strategies for certain antibiotics like tetracyclines.

Area of Science:

  • Hematology
  • Pharmacology
  • Oncology

Background:

  • Antibiotics possess off-target effects impacting mammalian cells beyond antimicrobial activity.
  • Hematologic toxicity, including cytopenias and bone marrow suppression, is a significant clinical manifestation of these effects.
  • This review investigates if the mechanisms causing normal hematopoietic cell injury can be leveraged against leukemia.

Purpose of the Study:

  • To synthesize evidence linking antibiotic-induced hematotoxicity to antileukemic activity.
  • To explore the potential repurposing of antibiotics for leukemia therapy based on shared biological pathways.
  • To identify specific antibiotic classes with preclinical evidence for antileukemic effects.

Main Methods:

  • Narrative review synthesizing molecular, clinical, and preclinical data.
  • Integrative framework linking cellular pathways (mitochondrial translation, oxidative phosphorylation, DNA stress, autophagy, apoptosis) to hematotoxicity and antileukemic activity.
  • Evaluation of evidence for various antibiotic classes (tetracyclines, macrolides, oxazolidinones, beta-lactams, etc.).

Main Results:

  • Selected tetracyclines, macrolides, and oxazolidinones show the strongest preclinical antileukemic potential linked to toxicity mechanisms.
  • Evidence for other antibiotic classes is more limited or hypothesis-generating.
  • Antibiotic-induced cytopenia does not automatically imply leukemia selectivity due to various confounding factors.

Conclusions:

  • Antibiotic hematotoxicity serves as a biologically informative signal for mechanism-based drug repurposing and combination strategies in leukemia.
  • Clinical translation requires rigorous validation of pharmacokinetics/pharmacodynamics, comparison with normal hematopoietic cells, and biomarker-driven selection.
  • Understanding shared toxicity and efficacy pathways is crucial for developing novel antibiotic-based leukemia treatments.
Keywords:
AntibioticsDrug interactionsDrug side effectHematologic toxicityLeukemiaRibosome

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