Access gates to the cell
With this research project, we hope to better understand how transport proteins influence the success of cancer therapy. With this knowledge, treatments can be designed more specifically, made more effective, and it may also be possible to better predict who will benefit from these therapies.
Motivation
New cancer treatments, such as antibody-drug conjugates (ADCs), are promising because they can deliver toxic chemotherapy directly to tumor cells. An ADC works by binding to a specific recognition site on a tumor cell. It is then taken up by the cell, allowing the drug to do its job. However, there is a problem. Once the ADC is inside, the drug still has to take an important step: it must escape from special compartments within the cell (the endosomes and lysosomes) to be truly effective.
It turns out that this step, also known as ‘endo-lysosomal escape’, is difficult for many drugs. Recent research shows that certain transport proteins (so-called SLC proteins), which can be seen as the gates of these compartments, can play an important role in this process. The presence and activity of such transport proteins can therefore determine how well a treatment works, or why some patients respond less well to ADC treatments.
Goal
The research project will focus on a limited number of selected transport proteins. Specifically, the project will focus on the role of lysosomal SLC transport proteins in the transport of ADCs and natural ligands from lysosomes to the cytosol in tumor cells.
Method
This project entails the design and synthesis of an innovative tracer targeting lysosomal transport proteins to accurately map transport processes. In parallel, fluorescent ADCs will be synthesized that are specifically suitable for investigating intracellular distribution and effectiveness. Efficacy will subsequently be determined by establishing a sensitive and reliable assay for quantitative measurement and evaluation of the transport of the aforementioned molecules from lysosomes to the cytosol in tumor cells.
Partners
HAN, QTM, Byondis
Drug Discovery
A start-up project in the drug discovery phase has between a 5-10% chance of making it to the research phase. At that stage, the success rate is about 10% to make it to market. Thus, a start-up drug project has a very small chance of eventually reaching 'the shelves'. The researchers of this professorship contribute to drug development.
