Projects / Programmes
Antiangiogenic siRNA for the treatment of advanced malignant melanoma
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B200 |
Biomedical sciences |
Cytology, oncology, cancerology |
Melanoma, Gene therapy, Antiangiogenic therapy, RNA interference, Electroporation, siRNA, DNA microarrays
Researchers (6)
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0302 |
Institute of Oncology Ljubljana |
Ljubljana |
5055733000 |
15,471 |
Abstract
Treatment of malignant melanoma poses a problem, because of its increasing incidence and lack of specific treatment approaches, predominantly in progressive disease. With increasing knowledge of biology of melanoma, many new targets for possible treatment are evolving. A specific adhesion molecule, known as melanoma cell adhesion molecule (MCAM/CD146) plays an important role in melanoma progression. It is involved in invasiveness and metastatic phenotype, as well as in angiogenesis. Therefore, specific ratgeted therapy to this molecule would be of great benefit for patients in advanced stages of the disease. Some studies have already reported on treatment approaches to CD146, using antibodies, however no study has reported yet on gene therapy targeted to CD146, either by siRNA or shRNA. Therefore, it is the aim of our study to design and test siRNA technique for CD146 silecing on melanoma cell lines in vito and in vivo on tumor model in mice. If succesful, this study woud thus provide a means of treating progressive melanoma, predominantly cutaneous dissemination. The technique of gene electrotransfer that is already in clinical testing would bring this treatment also to broader clinical use.
Significance for science
In the development of gene therapy one of the major focuses of research is the efficient and safe transduction/transfection of target cells. An ideal gene transfer method would allow introduction of a sufficient concentration of DNA into the desired target cells with minimal side effects. Electrogene therapy using electroporation has proved to be a good alternative to viral methods. However, the main disadvantage of this method is low transfection. In our project, we will further develop this method of transfection extending its use to the introduction of siRNA to target tissue. Namely, our research group has vast experience in the use of DNA plasmid electrotransfer and can therefore contribute substantially to the wider use of this method also for the transfection of siRNA other than siRNA against CD146. Furthermore, our research is focused on the development of a new treatment strategy for advanced stages of melanoma, targeting both tumor cells as well as tumor endothelial cells. By studying the process and mechanisms involved in antitumor effectiveness and expression of cancer-associated genes following the therapy, our research will contribute to the basic knowledge of biology of melanoma and tumor angiogenesis.
Significance for the country
The development of this technology, a gene therapy-based approach, is new and not fully developed in the world, as well as in Slovenia. Therefore, experience in the field will form the basis for development of other approaches based on gene electrotransfer.
Young researchers (PhD students) were trained during the project on the use of this technology, both at the stage of selection and preparation of the plasmids, as well as in the stage of its evaluation of antitumor effectiveness on experimental tumor models in vitro and in vivo.
Most important scientific results
Annual report
2008,
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
