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Hedgehog signalling proteins keep cancer stem cells alive

22 Jan 2018
Hedgehog signalling proteins keep cancer stem cells alive

Colon cancer is the third most common cancer and fourth most common cause of death worldwide.

Colon tumours consist of different types of cells, which play different roles in the growth of the tumour.

The development and spread of cancer is thought to be caused by a subpopulation of cells that possess stem cell characteristics, including the capacity for self-renewal, differentiation and therapy resistance.

These 'cancer stem cells' are also thought to be the source cancer recurrence following initial treatment success.

As part of OncoTrack project (an international consortium of scientists funded as part of the European Innovative Medicines Initiative), Dr. Joseph Regan and his colleagues at the Charité Comprehensive Cancer Center (CCCC) - working with scientists from the Max Planck Institute for Molecular Genetics, the Medical University of Graz and Bayer AG - investigated a treatment option aimed at treating cancers via the targeted elimination of cancer stem cells.

Their findings are published in the journal Cell Reports.

Potentially capable of significantly improving treatment outcomes, this approach requires an in-depth understanding of both the relevant cellular communication pathways within the stem cells, and of the genes regulating them.

As part of the current study, the researchers carried out genetic sequencing of the colon cancer stem cells and performed functional studies using both mouse models and 3D cell cultures from patient-derived cancer cells.

Their research revealed that cancer stem cell survival is controlled by a specific feature of the Hedgehog signalling pathway (SHH-PTCH1), which allows cells to respond to external signals in addition to inhibiting stem cell differentiation.

"The targeted inhibition of the Hedgehog signalling pathway, used in combination with other standard treatments to shrink tumours, may provide a new strategy for the elimination of cancer stem cells and the prevention of cancer recurrence," explains Dr. Regan.

Similar targeting of the Hedgehog signalling pathway has also produced promising results in other preclinical studies on pancreatic and breast cancer cells.

He adds: "Future research will set out to better define the downstream signalling components of the pathway and further investigate how Hedgehog signaling controls cancer stem cell survival."