Nat commun: self defeating! Cancer drugs actually promote the stem cell characteristics of cancer cells!

May 18, 2019 / bioun / - scientists from the German Cancer Research Center (DKFZ) and the Mannheim University Medical Center (mumc) now find that some cancer drugs (MEK inhibitors) can activate the Wnt signaling pathway promoting cancer in colorectal cancer cells This may lead to the accumulation of tumor cells with stem cell characteristics that are resistant to many therapies and may lead to cancer recurrence Therefore, the researchers provide a possible explanation for the ineffectiveness of these drugs in colorectal cancer Photo source: nature communications cells respond to external influences through biochemical reactions of Wnt signaling pathway Wnt signal plays an important role in many pathological processes as well as coordinating the early development of embryo Although the researchers initially thought that the over activation of Wnt signaling pathway was mainly related to the development of cancer, recent research results showed that the activity of Wnt could also affect cancer stem cells "Wnt signaling affects the balance between stem cell characteristic cells and differentiated cells, both in healthy bowel and colon cancers," explains Michael Boutros from DKFZ and the University of Heidelberg, Mannheim School of medicine "Wnt signaling pathway is particularly active in colorectal cancer stem cells and is responsible for maintaining stem cell characteristics According to Wnt activity, cancer cells can switch back and forth between stem cell state and differentiation state This plays a decisive role in the success of the treatment: cancer stem cells are believed to be the cause of relapse after the treatment Although "normal" cancer cells are often cut off by drugs, stem cells survive and become the culprit for future cancer recurrence Due to the high correlation between Wnt activity and disease process, the team of Michael Boutros and Matthias Ebert of mumc are studying whether some drugs used to target colon cancer will affect Wnt signal Many tumors are stimulated by mutations in the Ras signaling pathway that promotes growth These overactive Ras signals can be attenuated by MEK inhibitors However, these drugs have no effect on colorectal cancer, and researchers from Heidelberg and Mannheim now offer a possible explanation: they found that MEK inhibitors can stimulate Wnt activity in organ like cells cultured in mice and colorectal cancer patients At the same time, the gene activity of cancer cells transformed into the typical model of stem cells MEK inhibitors reduced the mitosis rate of intestinal tumors, but at the same time, tumor stem cells accumulated in the organelles of intestinal tumors Boutros and his colleagues now want to find out if specific drugs can be used to block the effects of MEK inhibitors on Wnt activity (bio Com) reference: Tianzuo Zhan et al MEK innovators activate Wnt signaling and induce stem cell plasticity in color cancer, nature communications (2019) Doi: 10.1038/s41467-019-09898-0