Projects / Programmes
Combination of electrochemotherapy with poly (adenosin diphosphate-ribose) polymerase inhibitor in treatment of breast cancer
| 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 |
electrochemotherapy, breast cancer, poly (adenosin diphosphate-ribose) polymerase inhibitor
Researchers (1)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
34373 |
PhD Maša Omerzel |
Medical sciences |
Head |
2019 - 2021 |
198 |
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
Electrochemotherapy is a local tumor ablation technique, based on a physical delivery method, electroporation. In electrochemotherapy, cisplatin and bleomycin are two most commonly used cytotoxic drugs. The cytotoxicity of cisplatin and bleomycin after electroporation can be potentiated up to 1000 times. Therefore, the amounts of the drug needed for good antitumor effectiveness are low, resulting in negligible treatment related adverse events. Bleomycin and cisplatin cytotoxicity is based on interactions with DNA, causing DNA breaks or adducts, respectively. Therefore, tumors of different histological types can be effectively treated with electrochemotherapy. bjective response (partial or complete response (CR) or stable disease) of the skin tumors is achieved in approximately 80% of the patients after treatment with electrochemotherapy. Nevertheless, electrochemotherapy has different effectiveness in different histological types of tumors. It is most effective in basal cell carcinoma with approximately 90% of CR, followed by melanoma with around 60-70% CR while in breast cancer there are only around 50% of CR.
Globally, breast cancer is the most frequently diagnosed malignancy and also a leading cause of cancer death in women, especially in developing countries. There are various histologic types of breast carcinoma that differ in microscopic appearance and biologic behavior as well as response to the treatment. Metastatic breast cancer patients are unlikely to be cured of their disease. The main goal of the treatment is to palliate symptoms, prolong survival, and maintain quality of life.
Currently PARP inhibitors are under EU approval process for treatment of breast cancer. Poly (adenosin diphosphate-ribose(ADP)) polymerase or PARP is a common name for the family of 18 proteins, enzymes responsible for catalyzing the reaction of adding the ADP-ribose to targeted proteins. PARP1 and 2 are required to repair single strand breaks (SSBs). PARP1 is also involved in repair of double strand breaks (DSBs) and in the replication forks. All clinically used PARP inhibitors inhibit both, PARP1 and PARP2 enzymes. PARP inhibitors as a monotherapy has already been approved for the treatment of ovarian, BRCA mutated cancer and are currently under approval process in the EU for the treatment of metastatic HER2 negative, BRCA mutated breast cancer. PARP inhibitors have already been tested with several systemic cytotoxic drugs, including cisplatin, but the combination caused higher frequency of adverse events, including substantial toxicity, due to high doses of the drugs, which have to be used to achieve an effective therapy.
Thus, a promising approach would be to combine electrochemotherapy with cisplatin and/or bleomycin with PARP inhibitor for the treatment of breast cancer metastases. In electrochemotherapy low doses of cisplatin or bleomycin are used, which cause no or minimal side effects. However, in breast cancer metastases electrochemotherapy alone exhibit low response rates (50% CR). Thus combination of electrochemotherapy with PARP inhibitor, which would inhibit the repair mechanisms after electrochemotherapy would most likely potentiate its effectiveness.
Significance for science
The results will be highly relevant for the treatment of skin metastases of breast cancer with electrochemotherapy, since the combination could potentially contribute to a higher number of complete tumour regressions. The confirmation that PARP inhibitors can potentiate electrochemotherapy would open up a whole new are of clinical use. Combination of electrochemotherapy and PARP inhibitors could substantially benefit patients with otherwise poorly treatable metastases and improve their quality of life.
Therefore promising results could lead to clinical testing of the combination at the national level (Institute of Oncology Ljubljana), as well as at the international level (the European INSPECT group) and subsequent introduction into clinical practice.
Significance for the country
The results will be highly relevant for the treatment of skin metastases of breast cancer with electrochemotherapy, since the combination could potentially contribute to a higher number of complete tumour regressions. The confirmation that PARP inhibitors can potentiate electrochemotherapy would open up a whole new are of clinical use. Combination of electrochemotherapy and PARP inhibitors could substantially benefit patients with otherwise poorly treatable metastases and improve their quality of life.
Therefore promising results could lead to clinical testing of the combination at the national level (Institute of Oncology Ljubljana), as well as at the international level (the European INSPECT group) and subsequent introduction into clinical practice.
Most important scientific results
Interim report
Most important socioeconomically and culturally relevant results
