Research group Caroline Palm Apergi

We are investigating Plk1 expression in childhood cancer patients. Our aim is to develop more specific treatments by targeting Plk1 with novel oligonucleotides and small molecules.

Research focus

Leukemia is the most common type of pediatric cancer and responsible for the highest proportion of death in children with cancer. Epidemiological studies of childhood cancer survivors have revealed an alarmingly high incidence of chronic health disabilities after treatment. Therefore, more specific and personalized therapies need to be developed. Polo-like kinase 1 (Plk1) is a serine/threonine kinase that plays a key role in various events during mitosis. It is overexpressed in many human solid tumors such as ovarian and breast cancer and recently found to be overexpressed in leukemia. Although several small molecules have been developed to inhibit the Plk1 protein, they are not specific but also inhibit other proteins. Depletion of Plk1 by RNA interference (RNAi) is specific and results in G2-arrest and apoptosis in tumor cells. However, the biggest barrier for RNAi therapeutics has been to find a delivery vehicle that can transport the active short interfering RNA (siRNA) across the cell membrane into the cytoplasm where it will exert its effect.

We are working with RNAi prodrugs that enter cells without any delivery vehicle and are cleaved by cytoplasmic enzymes inside cells into wild type siRNA that induce target mRNA cleavage. Our aim is to study Plk1 with RNAi prodrugs in comparison to small molecule inhibitors in samples from cancer patients and healthy donors to analyze if tumor cells, and not healthy cells, undergo apoptosis after Plk1 depletion. We are also investigating the mechanism by which non-transformed cells may survive Plk1 depletion and if other members of the Plk family are involved.


Selected publications