5 PhD positions in Cat4Cancer at University of Amsterdam

Every year in the Netherlands some 500 to 700 people are diagnosed with glioblastoma. Neither surgery, radiotherapy, nor chemotherapy have yet provided a cure for this form of brain cancer. The challenge faced by surgical and radiotherapy teams is that the tumours are not sharply defined and invade deep into the surrounding brain tissue.

The challenge for drug-based therapy is that glioblastoma cells are very effective in developing resistance. Even novel immunotherapy approaches – which have proved impressively successful in other solid tumours – have failed in the case of glioblastoma. This is largely due to a highly suppressive tumour microenvironment, where the so-called tumour-associated macrophages effectively ‘hijack’ the local immune response. In search of a solution, the Cat4CanCenter project takes a radically new approach. It combines the efforts of Prof. Joost Reek, an expert in catalysis at the UvA, Prof. Alexander Kros of Leiden University, specialising in drug delivery, and Dr Leila Akkari, a cancer immunologist at the Netherlands Cancer Institute (NKI) and Oncode Institute. Together, they propose a pioneering form of chemotherapy where active, toxic drugs are synthesised in the tumour environment itself. To enable this, first a molecular catalyst is delivered into the tumour tissue using lipid nanoparticles. Next, so-called pro-drug molecules are administered. Finally, the catalyst converts these non-toxic precursors into active drugs that will fight the glioblastoma ‘from within’.
In the context of this large program, the Homkat group currently has five PhD positions available and two post-doc positions available to design caged catalysts that will perform the synthesis of the desired drug molecules. In recent years the Homkat team has developed caged catalysts that allow metal-catalyzed synthesis in a biological environment. They now function in an aqueous environment, in the presence of biological molecules and even in living cells. By designing the cage so that is has affinity for the prodrug, we can make the catalyst operate in an enzyme-like fashion, boosting the conversion efficiency at low concentrations. In this program we need to make sure we can synthesise a whole range of drug molecules to combat all aspects of glioblastoma rapid growth, which involves the development of a large toolbox of caged catalysts for a variety of transformations. The research will be performed in close collaborations with the projects that are developed in Leiden and at NKI in the context of the ERC synergy program cat4cancer.