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Drug induced perturbations in tumor blood flow: therapeutic potential and possible limitations
D J Chaplin1, C E Peters, M R Horsman
1Medical Biophysics Unit, B.C. Cancer Research Centre, Vancouver, Canada.
Abstract:
Chemical modulation of tumor blood flow has until recently received relatively little attention as a therapeutic tool. Developments in the last few years, both in technology and in drug development, have changed this perspective. Fluorescence activated cell sorting techniques have provided evidence for the existence of acutely hypoxic cells resulting from transient fluctuations in microregional tumor blood flow in experimental tumor systems. We have used such techniques to assess the effects of three systemically administered agents, nicotinamide, flunarazine and Flusol-DA, on the amount of acute hypoxia in the SCCVII tumor. The most effective agent identified in this study is the benzamide analog nicotinamide. We suggest that compounds which modulate such hypoxia could well have a role in radiation therapy, particularly when combined with techniques which increase the oxygen carrying capacity of the blood. The potential of tumor blood flow reduction to improve the effectiveness of bioreductive agents administered alone or in combination with radiation and/or hyperthermia, is well established in experimental systems. Further data are presented, which show that combining hydralazine and the beta-blocker propranolol can provide greater reduction in tumor blood flow than observed with hydralazine alone. Potential limitations of drug induced reduction in tumor blood flow are discussed including the possibility of inducing hypoxia in normal tissues.
Insights
Nicotinamide effectively reduces acute tumor hypoxia, a key factor in cancer treatment. This finding suggests potential roles for hypoxia-modulating agents in radiation therapy and other cancer treatments.
Area of Science:
- Oncology
- Cancer Research
- Tumor Microenvironment
Background:
- Chemical modulation of tumor blood flow is an emerging therapeutic strategy.
- Acute hypoxia in tumors arises from fluctuations in microregional blood flow.
- Fluorescence activated cell sorting (FACS) detects acutely hypoxic cells.
Purpose of the Study:
- To evaluate the impact of systemically administered agents on acute hypoxia in SCCVII tumors.
- To identify effective agents for modulating tumor blood flow and hypoxia.
Main Methods:
- Utilized FACS techniques to quantify acute hypoxia.
- Assessed the effects of nicotinamide, flunarazine, and Flusol-DA on SCCVII tumors.
- Investigated combined hydralazine and propranolol for tumor blood flow reduction.
Main Results:
- Nicotinamide was the most effective agent in reducing acute hypoxia.
- Combined hydralazine and propranolol enhanced tumor blood flow reduction compared to hydralazine alone.
- Potential limitations include inducing hypoxia in normal tissues.
Conclusions:
- Nicotinamide shows promise for modulating tumor hypoxia in cancer therapy.
- Hypoxia-modulating compounds may enhance radiation therapy efficacy.
- Further research into tumor blood flow modulation is warranted.