Projects / Programmes
Development and evaluation of new approaches to cancer treatment
January 1, 2009
- December 31, 2014
Code |
Science |
Field |
Subfield |
3.04.00 |
Medical sciences |
Oncology |
|
Code |
Science |
Field |
B520 |
Biomedical sciences |
General pathology, pathological anatomy |
Code |
Science |
Field |
3.01 |
Medical and Health Sciences |
Basic medicine |
electrochemotherapy, electrogenetherapy, radiobiology, radiophysics, tumor physiology, immunohistochemistry
Researchers (33)
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 aim of the program was to develop and disseminate electroporation as medical application for treatment of tumors. Electrochemotherapy is ablation technique that has spread now into more than 140 cancer centers throughout the Europe. Our group, as pioneers in this field, has helped to develop its applications in treatment of cutaneous tumors. Currently we are translating this technology into the treatment of deep seated tumors. Also in this field we were the first that published the clinical study on 16 patients with liver metastases, and demonstrated safety and efficacy of the treatment. With further development in this field, our contribution in translating electrochemotherapy into treatment of other deep seated tumors has greatly contributed to the application of this technology in treatment of cancer. Gene therapy is innovative and rapidly growing treatment approach for cancer. Gene electrotransfer has been now recognized to have potential as delivery system, predominantly because of its safety compared to viral vectors. In our studies we developed plasmids encoding therapeutic molecules that would give antiangiogenic or immunomodulatory effectiveness. By further development and evaluation of the effectiveness we will foster this treatment approach into translational research, especially if it proves to be feasible and effective in combined treatment with radiation therapy. This activity has and will certainly have great impact on the role of gene therapy in cancer treatment. Both electrochemotherapy and gene electrotransfer have been translated into veterinary oncology, where we have been the leading actors so far. Therefore, we have on the basis of good pre-clinical work contributed to the development of this technology, to be implemented in treatment of animals, in Slovenia as well as internationally.
Significance for the country
Cancer incidence is steadily increasing, and the treatment of cancer patients is a growing financial burden for national health security systems. Specifically, because new targeted therapies are costly, however their effectiveness is below expectation. The impact of new therapeutic approach on health care system costs is an important factor in providing not only efficient but also less resource-intensive treatment approaches. With development of new therapeutic approaches as is electrochemotherapy we developed a new technology for treatment of cancer, which is electroporation based. The technology is relatively cheap and is applicable for drug delivery, and through its development it can replace some of the existing, more costly therapeutic approaches. Development of electrochemotherapy for the treatment of deep seated tumors will set the stage for its safe and efficient use in treatment also of other liver tumors and other deep seated tumors as well as. This method enables quality of life, predominantly those where other treatment modalities are exhausted, and may also increase their survival. Indirect impact of this project for society was the inclusion of the project in postgraduate studies in Slovenia as well as on the international level. According to this, doctoral students were involved in the project and the results were presented in their doctoral thesis. The results were regullarly presented at national and international conferences, and through this we promoted the Slovenenian knowlege, and were able to intergrate into the international collaborations. In addition, we are (co)authors of different patents and products, like: – coauthors of patent A cell based system for rapid detection and quantification of genotoxicity (Maja Cemazar, Gregor Sersa, Urska Kamensek ) – coauthors of patent Magnetofection of plasmid DNA with messenger gene into melanoma cells B16F1 cultivated in vitro with superparamagnetic nanoparticles in the presence of outer magnetic field (Sara Prijic, Gregor Sersa, Maja Cemazar ) – coauthor of inovation ECTplan - software for treatment planning of deep-seeted tumors with electrochemotherapy (Gregor Sersa)
Audiovisual sources (1)
Most important scientific results
Annual report
2009,
2010,
2011,
2012,
2013,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2009,
2010,
2011,
2012,
2013,
final report,
complete report on dLib.si