Scientists at HI-STEM have uncovered a yet unknown mechanism for therapy resistance in pancreatic cancer based on overexpression of the enzyme CYP3A5. The paper was published in Nature Medicine.

Read more:

·         DKFZ Press Release: Pancreatic Cancer: Enzyme renders tumors resistant

·         Citation: Noll, E.M., Eisen, C., Stenzinger, A., Espinet, E., Muckenhuber, A., Klein, C., Vogel, V., Klaus, B., Nadler, W., Rosli, C., Lutz, C., Kulke, M., Engelhardt, J., Zickgraf, F.M., Espinosa, O., Schlesner, M., Jiang, X.Q., Kopp-Schneider, A., Neuhaus, P., Bahra, M., Sinn, B.V., Eils, R., Giese, N.A., Hackert, T., Strobel, O., Werner, J., Buchler, M.W., Weichert, W., Trumpp, A., & Sprick, M.R. (2016). CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma. Nature Medicine, 22(3), 278-287. doi: 10.1038/nm.4038

 

 

February 15, 2016

In a process called diapause, many animal species delay the development of their embryos in order to ensure that their offspring is born at a possibly favorable time. Scientists from DKFZ and HI-STEM have now shown that this process is regulated by the MYC oncogene. If MYC is turned off in mice, embryonic stem cells and early embryos enter a reversible biochemical state of dormancy. However, this does not affect their ability to differentiate into any cell type of the body. When MYC is reactivated, the dormant embryos are able to develop into healthy animals. These findings have been published in the latest issue of “Cell” and were featured as the cover story.

Read more:

·         DKFZ Press Release

·         Citation: Scognamiglio, R., Cabezas-Wallscheid, N., Thier, M.C., Altamura, S., Reyes, A., Prendergast, A.M., Baumgartner, D., Carnevalli, L.S., Atzberger, A., Haas, S., von Paleske, L., Boroviak, T., Worsdorfer, P., Essers, M.A., Kloz, U., Eisenman, R.N., Edenhofer, F., Bertone, P., Huber, W., van der Hoeven, F., Smith, A., & Trumpp, A. (2016). Myc Depletion Induces a Pluripotent Dormant State Mimicking Diapause. Cell, 164(4), 668-680. doi: 10.1016/j.cell.2015.12.033

Cell

Dr. Dagmar Walter and Dr. Amelie Lier were awarded the 2015 Waltraud Lewenz prize for work carried out in the HI-STEM group, Experimental Hematology, led by Dr. Michael Milsom. The prize is awarded annually to young scientists who have published work judged to have furthered the understanding of cancer risk factors, cancer prevention or early detection of cancer. Drs. Walter and Lier were given this award based on the manuscript that they published in the prestigious journal Nature in April 2015, “Exit from dormancy provokes DNA damage-induced attrition in haematopoietic stem cells.”  The manuscript describes how environmental stress factors such as infection, inflammation and injury can lead to hematopoietic stem cell loss and the acquisition of potential cancer-causing mutations within the stem cell compartment.  As well as providing a new mechanism and model to study how cancer develops from the accumulation of DNA mutations within stem cells, this work also sheds new light on how stress-induced stem cell attrition is a likely driving force behind the normal ageing process.

References

Walter D., Lier A, Geiselhart A., Thalheimer F.B., Huntscha S., Sobotta M.C., Moehrle B., Brocks D., Bayindir I., Kaschutnig P., Müdder K., Klein C., Jauch A., Schroeder T., Geiger H., Dick T.P., Holland-Letz T., Schmezer P., Lane S.W., Rieger M.A., Essers M.A.G., Williams D.A.W., Trumpp A.and Milsom M.D. (2015). Exit from dormancy provokes DNA damage-induced attrition in haematopoietic stem cells. Nature, 520(7548): pp549-552).

 
 

Subcategories

News Milsom