Cancer is the subject of extensive research around the world. Many questions about the disease remain unanswered. How exactly does cancer start in the body, and how do tumours grow? The cancer stem cell theory could explain how some cancers work, and why patients suffer relapses.
What do we know?
Mutations in genes controlling cell division can cause healthy cells to become cancer cells. But it’s still not clear how small numbers of cancer cells grow into a tumour.
Only some cells in tumours continue to divide and multiply. This observation has led to two theories for how tumours grow. The ‘cancer stem cell model’ proposes that cancer stem cells make all other cells found in a tumour, like other types of stem cells in the body. Some tumour cells may undergo a period of division, but only cancer stem cells can make new cells indefinitely.
The ‘stochastic model’ suggests that many cells in a tumour divide, differentiate and contribute equally to the growth of that tumour.
What are researchers working on?
There are many unknowns about cancer stem cells. They may not even exist in all types of cancer. There is no definitive proof for one theory or the other yet and it is possible that different types of cancer may follow different theories. Researchers are looking for more direct evidence that cancer stem cells are present in tumours.
Researchers are trying to determine which cells become cancer cells. Can any cell become a cancer stem cell or do cancer stem cells come only from mutating genes in natural stem cells?
What are the challenges?
Researchers want to know what affects the behaviour of cancer stem cells. This means studying different genes, mutations, signals and environments. This is not easy; studying cancer stem cells often requires isolating the cells in a laboratory, where they may behave differently than inside the body.
Introduction to cancer
About cancer
In the healthy body, some cells can divide to produce new cells. This is a carefully controlled process that allows the body to grow, and to replace lost or damaged cells during adult life. In cancer, cells divide in an uncontrolled way, eventually forming an abnormal mass of cells called a tumour.
Cancer cells divide in an uncontrolled way because of mutations (changes) in their genes. Mutations accumulate as our cells divide and age. Many have little or no effect, but certain combinations of genetic mutations can lead to cancer.
How tumours grow
Despite intense research into cancer, it is not clear exactly how tumours grow. Cancers are very often made up of a mixture of different types of cells. Some cells divide repeatedly, while others appear to develop into more mature cell types that no longer divide. There are two main theories to explain this: the cancer stem cell theory and the stochastic (random) model of cancer growth.
Illustration 1: Cancer theories
The cancer stem cell theory suggests a clear hierarchy of cells within a tumour. The stochastic model says that tumour growth is a random process to which all cells can contribute.
The cancer stem cell theory suggests that tumours grow like normal tissues of the body: stem cells form the starting point of an organised system that produces new cells to make a tissue grow. According to this idea, tumours contain:
Cancer stem cells: these cells divide and drive tumour growth. These cells can self-renew (copy themselves) extensively, like other adult stem cells. They also produce transit-amplifying cells.
Transit-amplifying cells: like stem cells, these cells are undifferentiated. They self-renew a certain number of times, then stop dividing and differentiate (or 'mature') into specialised tumour cells.
Specialised tumour cells: these do not divide, and so do not contribute to tumour growth.
According to this idea, the cells in a tumour are in a strictly organised system. Cancer stem cells are the starting point for this organised system, giving rise to all other cancer cells.
The stochastic model of cancer growth gives a different possible explanation of tumour growth. This theory argues that all cancer cells have the same potential to grow and divide.Each cell chooses at random between self-renewal and differentiation. The cells in a tumour are not in an organised system – any cell has the same intrinsic potential to contribute to tumour growth.
Again, scientists are still researching how tumours start and grow in the body. Both of these theories may be correct. They may apply to different types of cancer, or to different stages of tumour development.
Current treatments
Evidence for cancer stem cells
There is no definitive proof in favour of either theory of cancer growth. However, an increasing amount of evidence suggests that the cancer stem cell theory holds true in some cases.
The first evidence in favour of cancer stem cells came from studies of human leukaemia. Researchers found that only a subset of leukaemic cells can cause leukaemia when transplanted into a healthy body, the key characteristic of cancer stem cells.
Since that discovery, many researchers have found cells with cancer stem cell characteristics in a great variety of human and mouse cancers, including breast, brain, skin, prostate and colonic cancers. In some types of cancer, such as colon cancer, the cells with cancer stem cell characteristics are rare. In other types of cancer, such as melanoma, a very large number of the tumour cells have cancer stem cell characteristics.
Cancer stem cells are controversial
The cancer stem cell theory is controversial among cancer researchers. Evidence for the existence of cancer stem cells relies mostly on experiments that involve breaking down a tumour, taking out specific cells and then transplanting them back into a body. This process does not exactly represent natural cancer growth.
To confirm whether these transplanted cells are really cancer stem cells, scientists have tracked individual cells within the resulting tumour. This approach has shown that individual cells do drive tumour growth within the environment of the body in certain cases (such as skin and colon cancers).
This type of analysis will need to be applied to different types of tumours, and different times points of cancer progression. This will allow scientists to assess the extent to which the cancer stem cell model holds true for different cancer types, and at different stages of the disease.
How might stem cells help?
Cancer stem cells and potential therapies
The cancer stem cell concept has important implications for cancer therapy. If cancer stem cells are responsible for maintaining tumour growth, then eliminating these cells would eventually cure the patient.It has also been suggested that cancer stem cells are more resistant to chemo- and radiotherapy than other cells in a tumour. This could be one cause of tumour relapse after therapy. Understanding how cancer stem cells resist medical therapy could lead to the development of new, more efficient cancer treatments.
Illustration 2: Cancer stem cells and therapy
If a cancer treatment destroys the bulk of a tumour but leaves behind cancer stem cells, then those cancer stem cells can continue to self-renew and can cause the tumour to regrow.
It has also been suggested that cancer stem cells are more resistant to chemo- and radiotherapy than other cells in a tumour. This could be one cause of tumour relapse after therapy.
Understanding how cancer stem cells resist medical therapy could lead to the development of new, more efficient cancer treatments.
Current research
Current research
More studies are needed to determine precisely how different cancers grow and how they resist medical therapy. Scientists are working to understand:
Do all tumours contain cancer stem cells? If not, what type of cell is the cell of origin, or starting point, for different cancers? How are cancer stem cells controlled? What genes, proteins or other molecules are involved in their development and behaviour?
Does the tumour’s immediate surroundings, or ‘microenvironment’, affect how cancer stem cells behave?
The answers to these questions will be important for future cancer treatment strategies.
