Projects / Programmes
A novel vascular targeted approach based on gene therapy silencing two independent
signaling pathways in combination with radiotherapy
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B200 |
Biomedical sciences |
Cytology, oncology, cancerology |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
gene therapy, CD105, CD146, vascular targeted therapy, irradiation
Researchers (1)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
35355 |
PhD Monika Savarin |
Medical sciences |
Head |
2019 - 2022 |
62 |
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0302 |
Institute of Oncology Ljubljana |
Ljubljana |
5055733000 |
15,472 |
Abstract
For normal development, growth and metastasis, a tumor needs its own blood vessels, which ensure consistent flow of nutrients, metabolites and oxygen. With vascular targeted therapies, we actively affect the tumor's blood vessels and indirectly on the tumor growth. Vessel modulation can improve oxygenation and then, by irradiating such tumor mass, a significantly better anti-tumor effect of combined therapies is achieved. Furthermore, a combination of therapies can also stimulate the immune system and the formation of long-lasting immune memory.
Combining radiotherapy and vascular-targeted therapies has a promising future in oncology. By silencing two important signal pathways in the tumor vasculature, a significant tumor growth control could be achieved. For a longer and more specific effect, we will make a plasmid that will encode for two functional shRNAs, CD105 and CD146, which will silence the expression of two different targets of tumor vasculature. Furthermore, in order to ensure safety for the user and the environment (European Medicines Agency recommendations), we will construct a plasmid with no antibiotic resistance. In this way, we will prevent the smallest possibility of horizontal transmission of antibiotic resistance to commensal bacteria.
By combining specific and safe gene electrotransfer with radiation, we will achieve a significant anti-tumor effect that can stimulate the immune system against a particular tumor system. Elucidated mechanisms of the therapy will also help to further establish a safe and effective new generation therapy.
Significance for science
The gene therapy is promising approach in the area of cancer treatment. In recent years, lots of projects and clinical trials ongoing are leaning towards safer and more specific delivery systems. Among therapeutic approaches, a vascular targeted gene therapy hold a great promise with modulation of tumor vasculature, which can affect tumor growth and development. Furthermore, this therapy can be combined with standard tumor treatment modalities, as radiation, and can lead to greater therapeutic outcome. By using specific plasmid, targeting two independent signaling pathways of tumor vasculature, one can achieve significant impact on vasculature and tumors themselves. To obtain higher specificity and safety, we will make a plasmid devoid of gene for antibiotic resistance. Therefore, the plasmid will be ready for safe implication in further potential clinical studies. Combining vascular targeted gene therapy and irradiation can significantly improve therapeutic outcome and can also affect modulation of immune response and its memory. Development of such therapeutic approaches and exploring mechanistic pathways can lead to greater findings and better understanding of cancer signaling pathways.
Significance for the country
The gene therapy is promising approach in the area of cancer treatment. In recent years, lots of projects and clinical trials ongoing are leaning towards safer and more specific delivery systems. Among therapeutic approaches, a vascular targeted gene therapy hold a great promise with modulation of tumor vasculature, which can affect tumor growth and development. Furthermore, this therapy can be combined with standard tumor treatment modalities, as radiation, and can lead to greater therapeutic outcome. By using specific plasmid, targeting two independent signaling pathways of tumor vasculature, one can achieve significant impact on vasculature and tumors themselves. To obtain higher specificity and safety, we will make a plasmid devoid of gene for antibiotic resistance. Therefore, the plasmid will be ready for safe implication in further potential clinical studies. Combining vascular targeted gene therapy and irradiation can significantly improve therapeutic outcome and can also affect modulation of immune response and its memory. Development of such therapeutic approaches and exploring mechanistic pathways can lead to greater findings and better understanding of cancer signaling pathways.
