Thesis topic proposal
Péter Hamar
Breast cancer treatment modalities: identification of cancerangiogenetic and -immunologic targets.


Institute: Semmelweis University, Budapest
theoretical medicine
Doctoral School of Basic and Translational Medicine

Thesis supervisor: Péter Hamar
Location of studies (in Hungarian): Semmelweis Egyetem
Abbreviation of location of studies: SE

Description of the research topic:

Description of the research topic:
Research topic: Despite enormous efforts to fight cancer, no effective treatment has been developed yet. New improvements in the field of tumor therapy research are directed towards activating the immune system. Oncotherm procedure is a new method in oncological hyperthermia (trade name: oncotherm, generic name: modulated electro hyperthermia (mEHT), which method has been developed from the original idea to the realization within Hungary. By using the oncothermia method, all results gained through animal testing and human examinations suggests, that the therapy is able to cause immunogenic death of tumor cells and thus induce a tumor specific local immune reaction. With the simultaneous use of a properly selected immune stimulation treatments, the local immune reaction can be turned into a systemic progressive reaction against the tumor, making it possible to control generalized metastatic tumors.
The primary aim of the planned research is to clarify the nature of the local and systemic immune reaction processes. By gaining the knowledge about the nature of the local and systemic immune processes, the oncothermic method can be optimized, possible side effects can be prevented, widening its clinical application. The project aims to investigate the protein and gene expression responses caused by mEHT intervention, at the cellular and tissue level, as well as the examination of the clinically demonstrable results. The ultimate goal is to develop an oncological treatment method, which integrates the latest research results with the most modern selective radio frequency heating methods.
Aim: The main purpose of the project is to exactly map the physiologic responses to mEHT as an adjuvant treatment combined with traditional tumor therapy (chemotherapy) regarding its effects on in-situ angiogenesis and immune modulation. Results gained by the research will contribute to a more effective onco-therapy, widening its clinical use.
Methods: The mEHT treatment can improve intensity and tumor specificity of conventional anti-tumor-therapies as additional (adjuvant) treatment. Therefore, we aim to combine mEHT treatment with other clinically used methods (chemo therapy, immune-checkpoint inhibition, targeted therapy) and with experimental phase treatments (angiogenesis inhibition, tumor infiltrating lymphocyte targeting, non-specific immunestimulation with IL-2 or IFN- cytokines).
To study the role of the immune system, we use mouse tumor cell lines implanted into syngeneic mouse strains. We monitor the growth of the tumor, metastasis formation, the effectiveness of the different therapies and the potential development of an abscopal effect with digital caliper and with in-vivo imaging. The magnitude of the immune response will be monitored by measuring blood sample cytokine levels (IL1,2,6,18, TNF-A).
To measure the extent of the angiogenesis, immunological cell death, tumor infiltrating lymphocyte and inflammasome activation, through the molecular biological examination of the tumors, we measure the gene and protein expression alterations.
Expected results: The main problem with malignant tumors is, that the natural defense mechanisms do not activate sufficiently to eliminate the disease.
The main goal of the researches is to develop such natural immune responses, which can overcome the actual tumor and can stimulate defense mechanisms to prevent tumor relapse. Nowadays, immune vaccination research is in the highlights, but the present form of vaccination is currently based solely on ex-vivo (extracorporeal laboratory immune treatment) processes. The current project would explore a completely new field by enhancing in-situ, in-vivo the immune effects, which would lead to a complex therapy to potentially treat micro- and macro- metastatic disease.

Number of students who can be accepted: 1

Deadline for application: 2019-12-31

All rights reserved © 2007, Hungarian Doctoral Council. Doctoral Council registration number at commissioner for data protection: 02003/0001. Program version: 2.2358 ( 2017. X. 31. )