Potentiation of anti-cancer drug activity at low intratumoral pH induced by the mitochondrial inhibitor m-iodobenzylguanidine (MIBG) and its analogue benzylguanidine (BG)
1999
Boosting Cancer Drug Effectiveness with Low pH
publication
Evidence: moderate
Author Information
Author(s): Kuin A, Aalders M, Lamfers M, Zuidam D J van, Essers M, Beijnen J H, Smets L A
Primary Institution: The Netherlands Cancer Institute
Hypothesis
Can reducing the pH in tumors enhance the effectiveness of anti-cancer drugs?
Conclusion
The study developed non-toxic methods to lower tumor pH, which improved the effectiveness of certain anti-cancer drugs.
Supporting Evidence
- The study confirmed enhanced cytotoxicity of chlorambucil at low extracellular pH.
- Melphalan and cisplatin required low intracellular pH for enhanced activation.
- A strong synergism was observed between nigericin and melphalan.
- Extracellular pH was effectively reduced to approximately 6.2.
- Tumor regrowth time increased from 5.7 days to 8.1 days with pH manipulation.
- Mitomycin C's tumor growth delay improved from 3.8 days to 5.2 days with combined interventions.
Takeaway
This study found that making the environment in tumors more acidic can help cancer drugs work better.
Methodology
The study used in vitro cell models and tumor-bearing mice to test the effects of pH manipulation on drug efficacy.
Limitations
The study primarily focused on specific drug interactions and may not generalize to all cancer types.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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