Projects / Programmes
Development and evaluation of new approaches to cancer treatment
July 1, 2004
- December 31, 2008
Code |
Science |
Field |
Subfield |
3.04.00 |
Medical sciences |
Oncology |
|
Code |
Science |
Field |
B520 |
Biomedical sciences |
General pathology, pathological anatomy |
electrochemotherapy, electrogenetherapy, radiobiology, radiophysics, tumor physiology, immunohistochemistry
Researchers (17)
Organisations (2)
Abstract
We are facing quick developments in cancer treatment. In the last decade, a vast amount of knowledge has been accumulated on the initiation and promotion of cancer cells as well as on how cancer cells control their environment and what are the interactions between the host and the tumor. This basic knowledge about cancer cells enables us to treat cancer. Without the knowledge about specific properties of cancer cells it would not be possible to develop new treatments because effectiveness of treatment rests on subtle differences between normal and cancer cells.
In order to introduce new treatments into every day clinical practice, we need a swift translation of knowledge from basic sciences into clinics. However, before clinical testing, it is mandatory to develop and evaluate new treatments in experimental oncology, whose main goals are to develop, either on cells in vitro and tumors in vivo on experimental animals, new treatments, discover their mechanisms of action, evaluate their effectiveness, and verify whether they are suitable for treating cancer patients with cancer.
Our research program can be divided into several fields of interest that are interrelated in many aspects. Electroporation is a physical method for delivering molecules into cells. It is also applied to deliver chemotherapeutics - electrochemotherapy, or naked DNA - electrogenetherapy. The aims of our research program are to apply electrochemotherapy in the treatment of cancer patients with cutaneous and subcutaneous tumors and to optimize electrogenetherapy to enter the first clinical trials. The effectiveness of radiation therapy can be potentiated by radiosensibilization, either with radiosensitizing drugs or gene therapy. Therefore, another goal is to search for some applications of electrochemotherapy and electrogenetherapy in combination with radiation therapy. Furthermore, we will apply some new radiation techniques, like three dimensional conformal radiation and intensity modulated radiotherapy (IMRT), and stereotactic radiosurgery. We will try to test their efficacy from physical and biological aspects. The knowledge about physiological parameters of the tumors is important for the prediction and for follow-up of the new treatments. Different techniques of tumor blood flow and oxygenation will be performed after the treatment with standard and newly developed approaches. Immunohistochemical staining enables the detection of specific molecules in the cells that are essential for the knowledge about biological behaviour of cancer cells. Nowadays, COX-2 and its inhibitors are very hot topics that will also be investigated in our research program.
This research program is complex, it is multidisciplinary and enables translational research in the described specific fields from preclinical testing into clinical practice.
Significance for science
The research program is devoted to development and translation of biomedical applications of electroporation in biomedicine and in treatment of cancer. Electroporation is used as a delivery system for various molecules in cells and tissues, including tumors. Electrochemotherapy enables enhanced drug delivery of bleomycin or cisplatin for an enhanced chemotherapeutic effect on localized tumors. Electrogene therapy also utilizes electroporation for plasmid DNA encoding reporter or therapeutic genes delivery into cells and tissues. In these two areas of research the research group has achieved exellent results and published the results in internationally renowned journals. Therefore, our research group is internationally recognized as one of the leading groups in this research area. Our main contributions in the development of the research field were: - Translation of electrochemotherapy into the treatment of melanoma metastases in human medicine. - Translation of electrochemotherapy into the treatment of primary tumors of small animals. - Basic resarch of electrogene therapy: evaluation of histological properties of tumors for effective eletrotransfection, the use of RNAi in treatment of colorectal cancer bearing K-ras mutation, evaluation of systemic gene therapy with IL-12 in treatment of tumors and metastases, development of plasmids encoding reporter and therapeutic genes under control of radioinducible promoters. - Basic research on the effect of electroporation and electrochemotherapy on tumor vasculature, evidence of vascular disrupting effects.
Significance for the country
Translational research has a great impact for development of new therapeutic approaches in oncology. The results of the program belong to translational reseach; electrochemoterapy is a treatment approach that has an impact on quality of life and also has an organ sparing effect. The research has contributed to technological development in cancer treatment. Electrochemotherapy is sometimes a treatment of choice, in other cases an alternative treatment to other treatment modalities, like surgery and radiotherapy. Electrochemotherapy, which has been developed in this program, is a recognized treatment and is in the doctrine for treatment of skin metastases of melanoma and is covered by the health insurance of the Republic of Slovenia.
Most important scientific results
Final report,
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Most important socioeconomically and culturally relevant results
Final report,
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