Cell-specific delivery of protein kinase inhibitors to the fibrotic liver

PhD ceremony: Ms. M.M. van Beuge, 16.15 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: Cell-specific delivery of protein kinase inhibitors to the fibrotic liver

Promotor(s): prof. K. Poelstra

Faculty: Mathematics and Natural Sciences

In her thesis Marike van Beuge has investigated the cell-specific targeting of various kinase inhibitors to the hepatic stellate cell, alone and in combination, and has found an improved efficacy of targeted inhibitors over the original untargeted drugs. Additionally, preliminary results indicate that the targeted drugs may not exhibit some of the side-effects displayed by kinase inhibitors.

Liver fibrosis is a growing problem worldwide. It is the result of various forms of chronic liver injury, such as those caused by hepatitis, chronic obesity or alcohol abuse. Fibrosis hinders the functioning of the liver, leading eventually to cirrhosis and possible other complications. Currently, there is no therapy capable of directly inhibiting the fibrotic process, although removal of the cause of fibrosis can lead to improvement in the functioning of the liver. Kinase inhibitors, which have been very successful in the treatment of cancer, offer the opportunity of effective fibrosis treatment, but are associated with side-effects, and so far none have been approved for clinical treatment of fibrotic diseases. Targeting of these inhibitors to the liver, and specifically to the central cell-type in liver fibrosis, the hepatic stellate cell, might improve the efficacy and safety of kinase inhibitor treatment.