One of the most striking features about tumors is that they have many, many mutations, all over the genome. To make things more complicated, not every cell in a tumor will have the same set of mutations. A tumor is a very heterogeneous (mixed) bunch of cells.

The presence of so many mutations led researchers to think about how cells could accumulate so many mutations so quickly.

We already know that DNA gets damaged all the time, but it’s normally repaired without problem. If the DNA repair mechanisms were somehow damaged, then those mutations would be able to accumulate, eventually triggering a tumor growth.

On the other hand, some scientists feel that all those mutations have accumulated slowly, over the life-time of the cell, not as a result of damaged DNA repair mechanisms. The longest lived cells in our bodies are stem cells. We wouldn’t consider all of them as true stem cells, which can produce all (totipotent = “total power”) the different types of cells in the body, but rather they can produce a certain subset of cells (pluripotent = “many power”). There are many different types of pluripotent stem cells in our bodies: in our nervous system, eyes, stomach, pancreas, liver, colon, skin, bone marrow, etc. Normally they count for less than 1% of the cells in an organ.

Whether toti- or pluri-potent, stem cells are exciting because they are:

• Long-lived
• Self-renewing, and
• Capable of multi-lineage differentiation (i.e. producing many different types of cells

They are responsible for replacing cells which die off. Because they are so long lived and because they can grow without limit, posit the Cancer Stem Cell (CSC) scientists, they slowly accumulate mutations, and act as the seed of tumor growth. There is growing evidence in support of the CSC scientists, but the topic is clearly still hotly debated. CSCs have already been found in breast, brain, cervix and lung tissue, among others. Check out this diagram to get an idea of how a stem cell should normally function and what happens when things go wrong:

Cancer Stem Cells

But why is that so exciting?

If all those cancers, and indeed many cancers, are caused by CSCs, it would change how cancers are treated. For instance, CSCs could be specifically targeted during treatment. The CSC scientists say that makes sense, because the reason cancer comes back after treatment is that those few progenitor cells (the CSCs) have not been destroyed. It’s important to destroy the tumor, but it more important to know that not all cells in a tumor act the same, some are benign and some can allow the tumor to grow again.

What do scientists propose?

Cancer treatments like chemotherapy target rapidly growing cells, reducing the size of tumors, but not necessarily eliminating the CSCs. Scientists argue that new therapies need to do both and the first step is being able to identify the CSCs in each tumor. For this scientists already have a handle of how these cells “look” like in a number of cancers (pancreatic, breast, prostrate, etc.). The current work is focused on being able to know how these cells “look” different from their neighbours, i.e. which genes are active or not. Therapies can then specifically target the destruction of those cells which are unique in the tissue.

Image and Citation:

KLONISCH, T., WIECHEC, E., HOMBACHKLONISCH, S., ANDE, S., WESSELBORG, S., SCHULZEOSTHOFF, K., & LOS, M. (2008). Cancer stem cell markers in common cancers – therapeutic implications Trends in Molecular Medicine, 14 (10), 450-460 DOI: 10.1016/j.molmed.2008.08.003