A Signalling Pathway That Keeps Cancer Stem Cells Alive

Scientists have investigated an alternative treatment focused on treating cancers by targeting the elimination of cancer stem cells

Colorectal cancer is a malignant tumor arising from the inner wall of the large intestine and caused due to development of cancer from the colon or rectum. Colon tumors consist of different varieties of cells, which play exclusive roles in the growth of the tumor. It is one of the most common causes of cancer all over the world.

The development and unfolding of most cancers is thought to be because of a subpopulation of cells that possess stem cell traits, consisting of the potential for self-renewal, differentiation and therapy resistance. these ‘most cancers stem cells’ are also assumed to be the source for cancer reappearance 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 an alternative treatment focused on treating cancers by targeting the elimination of cancer stem cells. This approach has the potential of substantially improving treatment outcomes and requires a detailed understanding of both the relevant cellular communication pathways within the stem cells as well as of the genes regulating them.

In their current research, the researchers performed genetic sequencing of the colon cancer stem cells and did the functional studies using both mouse models and 3D cell cultures from patient-derived cancer cells.  In Their research, they found out that cancer stem cell existence is regulated by a specific feature of the Hedgehog signaling pathway (SHH-PTCH1), which helps cells to respond to external signals in addition to inhibiting stem cell differentiation.

In the Hedgehog signaling pathway,  signaling molecule called Hedgehog (Hh) communicates information to embryonic cells required for proper cell differentiation. Different parts of the embryo have different concentrations of hedgehog signaling proteins. Diseases associated with the malfunction of this pathway include basal cell carcinoma

According to the Dr. Regan, if the hedgehog signaling pathway is inhibited and is combined with the treatment used to shrink a tumor, this may offer the new approach for eliminating cancer stem cells and cancer recurrence can also be prevented.

“Similar targeting of the Hedgehog signaling pathway has also produced promising results in other preclinical studies on pancreatic and breast cancer cells” says Dr. Regan.

“In the light of this, future research will set out to better define the downstream signaling components of the pathway and further investigate how Hedgehog signaling controls cancer stem cell survival” added Dr. Regan.