Tumoricidal effects of onconase on various tumors
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1Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6072, USA. ilee2@mail.med.upenn.edu
Background And Objectives:
The effects of Onconase (Onc) on the tumor growth in vitro and in vivo were examined. Because elevated tumor interstitial fluid pressure (TIFP) is one of the major causes of inadequate drug delivery into solid tumors, we tested if Onc could lower TIFP in solid tumors.
Methods:
We used several assays including a clonogenic assay and a growth delay assay for the determination of anti-tumoricidal effects of Onc. We also measured Onc-induced changes in several tumor physiological parameters.
Results:
Onc demonstrated cytotoxic effects in all eight exponentially growing cell lines in vitro. It effectively inhibited the growth of all four transplanted tumors in vivo, and significantly reduced TIFP in all four tumors. Onc also induced increases in tumor blood flow (TBF) as well as increases in median tumor oxygen partial pressure (pO(2)) in solid tumors.
Conclusions:
Onc showed anti-tumoral effects on various tumor cells in vitro as well as in vivo. We also gained some insight regarding the potential physiological benefit of Onc as a new therapeutic agent in cancer treatment. Due to increases in both TBF and tumor pO(2), Onc could be a potential candidate as a novel radiation enhancer; therefore, the study of the radiation response in vivo is warranted.
Insights
Onconase (Onc) exhibits potent anti-tumor effects, inhibiting cancer cell growth in vitro and in vivo. This novel agent also reduces tumor interstitial fluid pressure, improving drug delivery and potentially enhancing radiation therapy efficacy.
Area of Science:
- Oncology
- Cancer Therapeutics
- Tumor Physiology
Background:
- Elevated tumor interstitial fluid pressure (TIFP) impedes effective drug delivery in solid tumors.
- Onconase (Onc) is being investigated for its anti-cancer properties.
Purpose of the Study:
- To evaluate the anti-tumor effects of Onconase (Onc) in vitro and in vivo.
- To determine if Onc can reduce TIFP in solid tumors.
- To assess Onc's impact on tumor physiological parameters like blood flow and oxygenation.
Main Methods:
- Utilized clonogenic and growth delay assays to assess Onc's anti-tumoricidal effects.
- Measured Onc-induced changes in tumor physiological parameters, including TIFP, tumor blood flow (TBF), and tumor oxygen partial pressure (pO(2)).
Main Results:
- Onconase demonstrated significant cytotoxic effects against eight exponentially growing cancer cell lines in vitro.
- In vivo studies showed Onc effectively inhibited the growth of transplanted tumors and significantly reduced TIFP.
- Onc treatment led to increased tumor blood flow (TBF) and median tumor oxygen partial pressure (pO(2)).
Conclusions:
- Onconase exhibits broad anti-tumor activity against various cancer cells both in vitro and in vivo.
- Onc's ability to reduce TIFP suggests a potential mechanism for improving therapeutic drug delivery.
- Increased TBF and tumor pO(2) indicate Onconase's potential as a novel radiation enhancer, warranting further investigation into its combined use with radiation therapy.
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