Cancer Stem Cells
Accumulating data suggests that many human tumors are organized in cellular hierarchies initiated and maintained by a small population of self-renewing so called cancer stem cells. This was first demonstrated in acute myeloid leukemia (AML) but during recent years, cancer stem cells have also been demonstrated in other cancer types. These cells are not killed by conventional cancer therapy and thus it is critical to identify those cancer stem cells to be able to improved diagnostics and treatment of cancer.
Cancer stem cells in leukemia: Within the MAD for Cancer Program, a previously unexplored combination of strategies will be used to identify new cell surface markers on AML stem cells. By generating recombinant antibodies against a set of such markers, validating their clinical use, and providing in vivo proof-of-concept data in preclinical models for a targeted antibody-based therapy, novel diagnostic and therapeutic modalities for AML will be designed. Investigators at the Department of Clinical Genetics have a strong track record in identifying novel cell surface markers on leukemia stem cells and were the first to demonstrate the potential therapeutic use of recombinant antibodies directed against the marker IL1RAP (interleukin-1 receptor accessory protein) on cancer stem cells in chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). The strategy used to identify new therapeutic markers on leukemia stem cells will also be explored in other tumor types studied within the MAD for Cancer Program.
Cancer stem cells in solid tumors: Within the MAD for Cancer Program we aim to clarify the link between kidney cancer and the kidney progenitor cells, and to develop novel biomarkers for kidney cancer based on our understanding of adult kidney progenitor cells. This will be achieved by a detailed characterization of adult kidney progenitor cells; sequencing, manipulation of genes, identification of surface molecules allowing also for antibody-based immunotherapy, an area were we have a long-standing tradition. In addition, validation of preliminary findings of solute carrier molecules (usually used for drug-delivery) selectively expressed in tumor cells with the aim to develop imaging-led theranostic approaches of personalized treatment will be performed.
Furthermore, it is well known that solid tumors experience impaired oxygenation due to inadequate vascularization. This correlates to metastatic spread and aggressive disease in vivo. Numerous studies show that high levels of hypoxia inducible transcription factors, HIF-1α and HIF-2α, also correlate to aggressive tumor disease. In work performed by Division of Translational Cancer Research it is shows that the hypoxic state pushes neuroblastoma and breast cancer towards an immature, stem cell-like phenotype. Cells with high expression of HIF-2α have properties rendering the tumors aggressive behavior potentially being the neuroblastoma tumor stem cells. Within the MAD for Cancer Program we will, based on this, aim to design novel treatment options.