Cancer cell: Hierarchically structured tumors are directed by degenerate cancer stem cells
© Getty Images
© Getty Images
Breaking through the protective mechanisms
Medical researchers have very high hopes for healthy stem cells when it comes to diseases such as diabetes, muscular dystrophy, and Parkinson’s, which involve a loss of cells. Stem cells also have a “dark side”, however. If their genetically determined feedback loops are damaged by mutations, they can “run amok” and produce tumors. The fatal factor is that a perfect system of protective mechanisms continues safeguarding these cancer stem cells against destruction, just as it does normal stem cells. This makes them resistant to treatments such as radiation. Furthermore, cancer stem cells rarely divide themselves, so classic chemotherapy, which attacks rapidly dividing cells, does not have an impact on them. It is the “offspring” of the cancer cells that quickly reproduce and threaten the organism with their growth.
In 2001, Trumpp found himself for the first time on the search for the inscrutable mastermind behind cancer. At the time he was examining mice whose cancer genes had been altered, and he was able to prove that these genes affected some stem cells: “I remember that evening very clearly: I went out and bought a bottle of champagne. This was followed by an exciting time, in which I converted my laboratory to exclusively work with stem cells.”
Shortly after, another scientist became aware of this young field of research: Michael Wolf, Head of the Applied Immunology Research Group in the Oncology unit at Merck Serono. He heard of the articles published by the stem cell researchers and decided to look into the matter. “When I first heard of it, I felt like a window had just opened,” he says. “After 50 years of cancer research, there was still a considerable feeling of hopelessness. However, this concept could bring new hope for patients that are still incurable. Research in this area is currently expanding in leaps and bounds.”
Many questions remain unanswered, of course. It has been proven that leukemia is caused by cancerous stem cells, and there are clear indications that this also could be the case with breast cancer and brain tumors. Nevertheless, it still remains to be seen whether tumors are always caused by cancer stem cells. In addition, it will probably take several years until the new insights can be incorporated into effective treatments.
The research will certainly not fail due to a lack of determination on the part of scientists such as Trumpp and Wolf. At Merck, Anita Seshire has been supervising intensive work in the labs for two years now. In fact, Trumpp and his employees recently found out how to rouse blood stem cells and probably also leukemia stem cells from a state of hibernation that enables them to successfully protect themselves against all attacks. Trumpp hopes that if the stem cells are then attacked with customized active ingredients, it might be possible to completely eliminate the cancer. What’s especially interesting about these cases is that such active ingredients might already exist, but are simply unable to reach the tumor stem cells. To solve this problem, Trumpp is working together with Merck Serono in a joint project. This division of Merck, with its innovative, patent-protected medicines, provides Trumpp with new active ingredients, which he then uses to try and kill off the activated cancer stem cells. “We couldn’t otherwise get access to these substances,” says Trumpp. Using complex transplantation experiments with mice, he and his colleagues at HI-STEM want to find out what combination and sequence of substances might be effective. “There will never be just one active ingredient for a particular type of cancer,” says Trumpp. “That’s why clinical trials are so complicated and why we still have to gain very in-depth information before we can begin them.” The discovery of cancer stem cells could, however, prove to be a decisive step down this path.
Medical researchers have very high hopes for healthy stem cells when it comes to diseases such as diabetes, muscular dystrophy, and Parkinson’s, which involve a loss of cells. Stem cells also have a “dark side”, however. If their genetically determined feedback loops are damaged by mutations, they can “run amok” and produce tumors. The fatal factor is that a perfect system of protective mechanisms continues safeguarding these cancer stem cells against destruction, just as it does normal stem cells. This makes them resistant to treatments such as radiation. Furthermore, cancer stem cells rarely divide themselves, so classic chemotherapy, which attacks rapidly dividing cells, does not have an impact on them. It is the “offspring” of the cancer cells that quickly reproduce and threaten the organism with their growth.
In 2001, Trumpp found himself for the first time on the search for the inscrutable mastermind behind cancer. At the time he was examining mice whose cancer genes had been altered, and he was able to prove that these genes affected some stem cells: “I remember that evening very clearly: I went out and bought a bottle of champagne. This was followed by an exciting time, in which I converted my laboratory to exclusively work with stem cells.”
Shortly after, another scientist became aware of this young field of research: Michael Wolf, Head of the Applied Immunology Research Group in the Oncology unit at Merck Serono. He heard of the articles published by the stem cell researchers and decided to look into the matter. “When I first heard of it, I felt like a window had just opened,” he says. “After 50 years of cancer research, there was still a considerable feeling of hopelessness. However, this concept could bring new hope for patients that are still incurable. Research in this area is currently expanding in leaps and bounds.”
A specific mix of active ingredients for each type of cancer
Many questions remain unanswered, of course. It has been proven that leukemia is caused by cancerous stem cells, and there are clear indications that this also could be the case with breast cancer and brain tumors. Nevertheless, it still remains to be seen whether tumors are always caused by cancer stem cells. In addition, it will probably take several years until the new insights can be incorporated into effective treatments.
The research will certainly not fail due to a lack of determination on the part of scientists such as Trumpp and Wolf. At Merck, Anita Seshire has been supervising intensive work in the labs for two years now. In fact, Trumpp and his employees recently found out how to rouse blood stem cells and probably also leukemia stem cells from a state of hibernation that enables them to successfully protect themselves against all attacks. Trumpp hopes that if the stem cells are then attacked with customized active ingredients, it might be possible to completely eliminate the cancer. What’s especially interesting about these cases is that such active ingredients might already exist, but are simply unable to reach the tumor stem cells. To solve this problem, Trumpp is working together with Merck Serono in a joint project. This division of Merck, with its innovative, patent-protected medicines, provides Trumpp with new active ingredients, which he then uses to try and kill off the activated cancer stem cells. “We couldn’t otherwise get access to these substances,” says Trumpp. Using complex transplantation experiments with mice, he and his colleagues at HI-STEM want to find out what combination and sequence of substances might be effective. “There will never be just one active ingredient for a particular type of cancer,” says Trumpp. “That’s why clinical trials are so complicated and why we still have to gain very in-depth information before we can begin them.” The discovery of cancer stem cells could, however, prove to be a decisive step down this path.
