The molecular targeting group is headed by Professor Karl-Henning Kalland and has long experience in advanced molecular studies of gene expression regulation in normal cells, virus-infected cells and cancer cells.

A newly developed model of experimental stepwise prostate carcinogenesis is important in the group. Started from benign human prostate epithelial cells a series of progeny cell types with an accumulating number of cancer hallmarks were derived. The model now includes tumorigenic and metastatic cells in mice, it includes a step of epithelial to mesenchymal transition (EMT) and subpopulations of tumor initiating cells (TICs) and cancer stem cells (CSCs). All these cell types were obtained based upon transcriptional reprogramming during physiological adaptation and selection. Forensic grade DNA microsatellite analyses have verified the genetic authenticity of all cell lines of the model.

The experimental stepwise prostate carcinogenesis model is used in order to understand changes of gene expression at critical steps of carcinogenesis. This includes gene expression, microRNA and epigenetic switches at steps such as EMT and tumorigenesis and metastasis. Advanced technology of microarrays (Agilent platform of our group) and next generation sequencing and genome-wide analyses are coupled to functional assays. Lentiviral over-expression and knock-down technology, fluorescent reporter constructs and small molecular compounds are used in experimental designs.

The aim is to understand signal transduction pathway activation and hierarchies of transcriptional regulation which are associated with important cancer hallmarks of the model. Currently the IL6/STAT3 and WNT/Beta-catenin pathways and the transcription factors androgen receptor (AR), FOXA1, NKX3-1 and TP63 are focused.

The experimental model is also exploited in a Drug Discovery Program based upon panels of phytochemicals as part of collaboration with Chinese institutions. Additional small compound panels are screened for activity in the EMT program and for selective toxicity against the malignant cells of the model. Leading compound discovery is coupled to molecular target identification. The aim is to develop anti-cancer drugs in innovative combination strategies.

Our group has an ongoing initiative to identify and isolate circulating cancer cells from peripheral blood of cancer patients. The aim is to examine how malignant cells of our model capture essential features of circulating cancer cells.

One leg of the innovative combination strategies consists of the clinical implementation and development of a module of cryoimmunotherapy. This clinical trial has been motivated by the known heterogeneity of disseminated cancer cells and their ability to extensive transcriptional reprogramming plasticity, such as we have observed and studied in our experimental model.