Seek And Destroy: Targeting Cancer Stem Cells

Credit: Christina Tu / Sue & Bill Gross Stem Cell Research Center

We now know many cancers contain a population of 'cancer stem cells', which often escape treatment and cause later regression. Treating these cells could knock out cancer at its source. 

What are cancer stem cells? 

While it was once believed that each cell in a cancer could propagate a tumour, when experiments have removed and implanted tumour cells into healthy mice, the vast majority didn't form cancers. Only a small minority of cells were able to continue forming a tumour - so called cancer stem cells, or CSCs. 

Some scientists gradually began forming a theory that cancer originates, for the most part, from one stem cell that has undergone mutation. The differentiated cells that make up the bulk of your body have many more blocks and safety mechanisms that mean they must undergo multiple mutations to turn cancerous. Stem cells on the other hand are primed to divide. It's their job. The cancer stem cell theory suggested that a single stem cell undergoes a small number of mutations, perhaps even one or two alone, which then allows cancerous behaviour. 

Targeting these cells

While this doesn't explain every single cancer type and there is still debate in the field today, it's proved itself a promising target in many cancer types. Radiotherapy and chemotherapy can spare these cancer stem cells when they're in a quiescent, resting state. This can somehow protect them from treatment, but when they become active again they can start to form tumours once more. While it's clear cancer stem cells exist in many types of cancer, it's hard to find and target them.

Credit: Cosmo Bio

A team from Trinity College Dublin has discovered a way to activate dormant CSCs, making them easier to target and destroy. The tumour suppressor protein p53 is used to suspend cells in a quiescent state and prevent division. It often does this when cells become damaged, but it appears it also has a role in maintaining quiescence in CSCs. The team found that  another protein called PCL1 contributes to this p53 regulated 'hibernation', and that blocking its action could awaken the cells. 

"Often, treating a cancer patient with chemotherapy or radiation doesn't work out as planned. The tumour shrinks at first, but the cancer stem cells within can survive and eventually seed the growth of new, more aggressive cancers. When cancer stem cells are in this state of 'cellular quiescence', the treatments can really only be partially effective"

The discovery that PCL1 boosts and maintains this quiescence opens the way to drugs designed to block or inhibit the process; awakening dormant cells and rendering them vulnerable to treatment. 

Activating CSCs could make conventional cancer therapies far more effective

"Our discovery that PCL1 has acquired a new function during the relatively recent evolution of mammals was very interesting. We are now excited about using this new knowledge to develop a strategy to target cancer stem cells by knocking them out of their dormant state, thereby making them more amenable to standard chemotherapy and radiotherapy"

 

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