Cancer Stem Cells

We begin life as a bundle of embryonic stem cells, which divide and differentiate until you have all the various cell types required to make the many tissues and organs of the human body. In adulthood some stem cells remain to maintain the body's diverse cell types during growth, injury and aging. These adult stem cells are less adaptable than the embryonic stem cells which can form any tissue type, adult stem cells exist in multiple sets each specialised for maintaining a particular tissue types. Tissues that have been identified to contain stem cells include bone marrow, blood, brain, muscle, skin and liver. Most other tissues are also likely to contain stem cells, but their number is tiny in comparison to the normal cell population and this makes their identification difficult.

In recent years it has become evident that cancers also have tiny populations of stem cells that produce the main body of the cancer. During cancer treatment, the chemotherapy drugs and radiation therapy are often highly successful in reducing the size of the tumor, and often the cancer seems to be totally cured. However, several months or years later, the cancer often returns. This could only happen if a population of cancer cells survived the therapy, that population is likely to be very small, small enough not to be seen by a surgeon or a radiographer, it could even be a single cell. These cells are thought to be the cancer stem cells, indeed it has been shown that the cancer stem cells are highly resistant to radiation death, and are often resistant to chemotherapy too.

It would seem to make sense that cancer originates from adult stem cells that have mutated to form cancer stem cells. Adult stem cells are constantly copying their DNA and dividing to produce a specialist cell and a replacement stem cell to maintain the stem cell population. They divide like this constantly throughout your whole life to maintain your body. Each time the DNA is replicated it is vulnerable to copying errors, and over a lifetime may acquire mutations in tumor suppressor genes, inactivating the genes that control cell growth.

If current chemotherapy drugs are not effective against the cancer stem cells, it is because the majority of cancer research to date has been performed using cancer cells which are more than likely the product of the stem cells, but not the stem cells themselves. This means the drugs have been developed to be effective against the body of the tumor, but may not be targeting the cancer stem cells that drive the growth. While destroying the main body of a tumor is still useful in alleviating the pain and problems of having large masses interfering with the organs, the cancer stem cells will also need to be targeted to achieve a true cure.

Much work is currently underway at research institutions around the globe to better identify these cancer stem cells, their genetics and molecular mechanisms. For example this week the pharmaceutical giant Eli Lilly began a collaboration between its Singaporean Centre for Drug Discovery and Singapore's National Neuroscience Institute and Institute for Clinical Sciences. This collaboration has the aim of utilising newly isolated brain tumor stem cells to discover new drugs that will be effective in targeting the stem cells that cause brain tumors.

Meanwhile in Cincinnati, researchers at the Cincinnati Children's Hospital Medical Centre have recently been exploring the involvement of cancer stem cells in neuroblastoma, a cancer of the nervous system. They are also experimenting with a potential virus therapy. This virus is a specially modified herpes virus that could target neuroblastoma stem cells and kill them by infection.

Efforts in recent decades have given us hundreds of chemotherapy drugs of varying effectiveness. But until now we have been measuring their success against the general tumor mass and not on the cancer stem cells. With greater understanding of the biology of cancer stem cells we will be able to target them specifically and ensure the whole tumor is treated. This should improve the survival of cancer patients and reduce the rates of relapse following therapy.