July 8, 2022
Keio University School of Medicine
A research group led by Researcher Yuki Ota, Senior Lecturer Masayuki Fujii, and Professor Toshiro Sato of The Sakaguchi Laboratory (Organoid Medicine) at the Keio University School of Medicine has for the first time elucidated the mechanism by which human cancer stem cells, which drive the growth of colorectal cancer, survive chemotherapy and lead to tumor relapse and recurrence. While the existence of cancer stem cells that are not killed by chemotherapy has been considered a cause of tumor relapse and recurrence, the details have remained unclear. The research group has now successfully developed a technique to transplant human colorectal cancer into mice and observe its behavior in real time. Using this technique, they revealed that some cancer stem cells enter a dormant state (a non-proliferative state), allowing them to survive chemotherapy and undergo clonal expansion. Furthermore, they discovered that cancer stem cells maintain their dormant state by adhering to the extracellular matrix (basement membrane). They also found that when this adhesion to the basement membrane weakens, the dormant cancer stem cells resume proliferation along with the activation of the YAP signal. The research group therefore confirmed in animal models that a drug that inhibits the YAP signal suppresses the regrowth of cancer stem cells after chemotherapy, delaying tumor relapse and recurrence. These findings are expected to lead to the development of new therapies targeting tumor relapse and recurrence, which are key determinants of prognosis in colorectal cancer.
The results of this study were published in the international scientific journal Nature on July 7, 2022 (UK time).
The full press release is available below.