According to a study published in the November issue of Cell Stem Cell, the world’s leading journal in stem cell research, Prof. Christopher Heeschen and his team from the Clinical Research Program at the Spanish National Cancer Research Center (CNIO) have successfully found new treatments for pancreatic cancer stem cells as the cause of a devastating disease. Pancreatic cancer is one of the most deadly diseases and its prevalence continues to increase.
Investigations led by Dr. Enza Lonardo in the Stem Cells & Cancer Group show conclusive evidence for the re-activation of a developmental pathway in cancer stem cells similar to those found in embryonic stem cells. The team succeeded in identifying the embryonic factors Nodal and Activin, also called morphogens , as two critical components that regulate two-way communication between cancer stem cells and an embryonic-like microenvironment, drastically increasing their plasticity and aggressiveness. Nodal and Activin are responsible for maintaining the pluripotency of human embryonic stem cells.
Researchers noted with interest that apart from being a driving factor in pancreatic cancer stem cells, the Nodal/Activin pathway also drives pancreatic stellate cells. Stellate cells are abundantly present in the stroma that surrounds pancreatic cancer cells, and could be a supportive niche for cancer stem cells. Results from preclinical investigations conducted by the researchers indicate that the cancer stem cell compartment can be critically changed by restriction of this pathway resulting in chemo-sensitization of the cancer stem cells. According to the investigators, long-term survival could be accomplished when chemotherapy for destroying the differentiated cancer cells is combined with targeting of the stroma (promoted by an additional developmental pathway called hedgehog).
The scientists have subsequently found that the Nodal/Activin pathway blocks metastasis progression, as well as the development of tumors. Cancer stem cells rely heavily on the activity of an embryonic pathway, according to new data. Animal studies have shown that clinically appropriate mouse models have considerably better outcomes with Nodal/Activin inhibitors if their pathway is combined with an adequate reduction of the stroma to destroy the tumor’s microenvironment. If the tumor’s microenvironment is destroyed, medications can get to the cancer stem cells more easily.
Dr. Heeschen and his team are currently focusing on the clinical translation of this promising novel treatment modailty.
Written by Grace Rattue