Research

Tunneling nanotubes for innovative urinary bladder cancer treatments

Code:

J3-7494

Range:

01. January 2016 - 31. December 2018

Range:

0,10 FTE

Leader:

Petra Kocbek

Field:

3.04 Medical Sciences/Oncology

Abstract:

Scientific background and problem introduction Urinary bladder cancer is 6th among all cancers worldwide and 1/3 of urinary bladder cancer emerges as multifocal tumours at different sites of the urothelium, e.g. epithelium which represents effective blood-urine barrier. Treatment usually includes the resection of the tumours during the transurethral resection of the urinary bladder. Despite the progress of surgical and chemotherapeutical approaches, the prognosis is still poor, mostly due to high recurrence rate of these tumours. Moreover, 50% of patients with invasive urinary bladder cancer die within five years from diagnosis. Intercellular communication is essential for tissue development during embryogenesis and growth, for tissue maintenance during adulthood and also for cancer cells survival and tumour development. One of the mechanisms for intercellular communication is long membrane protrusions named tunnelling membrane nanotubes – TnT. In the project we examine mechanisms that enable the transfer of biocompatible composite nanoparticles and signal molecules by TnT, which will significantly contribute to the understanding of this relatively new form, however widespread intercellular communication. Based on the obtained results, we will develop innovative approaches for the treatment of urinary bladder cancer. Aims of the project are: 1) analysis of cellular-biological mechanisms of TnT formation, their molecular structure and ultrastructure and also their function in cancer and normal urothelial cells, and 2) development of innovative approach for treatment of urinary bladder cancer combining advanced diagnostics, targeted application, and transfer of anticancer drug. This targeted anticancer therapy will be founded on the use of TnT a) as targets for anticancer drugs, which will inhibit the formation of TnT and b) as a route for transfer of anticancer drugs between cells. For targeted drug delivery and for sustained therapeutic effect, we will develop biocompatible composite nanoparticles and specific fusion gene constructs. Execution and management of the project: The project is organized sequentially towards the final goal, i.e. preclinical testing of suggested targeted therapy on biomimetic in vitro models and by orthotopic in vivo models of bladder cancer. The project is divided into the three workpackages and it is presented graphically in the attached file (Graphical Abstract-TnT 2015_angl.pdf). The work on the project will be executed at the laboratories of 7 partners participating in the project. The consortium provides key elements guaranteeing the success of the project, namely, the choice of excellent researchers, complementary expertise and experience, proven track record of previous successful collaborations between partners, and all the necessary equipment available. Besides the scientific work the project leader will be in charge of the technological aspect and will monitor the project, overseeing the implementation of the work on the basis of the results and provide high-quality follow-up of the work packages to the project completion. The management and coordination of the project will be assured by regular meetings and constant communication with partners on the project. Relevance and potential impact of the results The main goal of our project is focused on the maintaining and improvement of the quality of life. Project is very ambitiously constructed and aims to move boundaries of knowledge at the field of cell biology with regards to innovative approaches of bladder cancer treatment as well as wider and relevant also for treatment of other cancer diseases, which present one of the biggest health, social, and economical burdens for the society. The chances of the translation of the project results into clinical practice and to the market are high, also because of the active participation of a clinical partner in the project as the clinical partner presents the final user.