The root of all evil

Andreas Trumpp is convinced that successful cancer treatment can be effected only, if both the "normal" cancer cells and the "parent cells" are destroyed in a targeted manner. Yet since cancer stem cells account for only a fraction of the tumour, depending on the kind of tumour and stage, searching for them is akin to finding the needle in the haystack. "We develop methods for identifying the relatively rare tumour stem cells. This is the only way to analyse them in detail and to develop treatments for targeted combating", describes Trumpp the goal of his research. For this, he and his team first need to arrive at a detailed understanding of the biology of the cancer stem cells. For instance, they search for external distinctive features, so-called biomarkers, which are characteristic only of cancer stem cells of a certain kind of tumour. Moreover, Trumpp and his colleagues want to find out how to rouse the cells from their deep sleep: "If we could awaken these sleepers, it might be possible to eliminate cancer stem cells also with traditional forms of treatment and thus to treat the whole disease more effectively." The support base would be destroyed. Trumpp and his team have already identified specific messengers that awaken dormant healthy blood stem cells. Using the same signal, they could also activate dormant neoplastic blood cancer stem cells to render them more susceptible to subsequent treatment.

Trumpp and his team recently celebrated another success – combating metastases. Individual cancer cells have the ability to split off from their main tumour and to disseminate via the blood, spreading throughout the patient's body. Researchers call these circulating cancer cells. They are made responsible for the formation of metastases. So far, however, scientific proof of this was unavailable. "We were convinced that only a few of these circulating cancer cells were able to create new metastases in other organs", says Trumpp. After all, many patients do not develop any metastases at all, even though cancer cells do circulate in their blood. "So these must be cancer cells with very specific abilities. We assumed that these were metastasis-inducing stem cells, which derive from the cancer stem cells of the primary tumour." Indeed, Trumpp and his colleagues discovered circulating cancer cells in the blood of breast cancer patients that initiate metastases and feature cancer stem cell characteristics. The Heidelberg researchers have made progress also with regards to how to combat these cells. They discovered three characteristic proteins on the surface of the circulating metastasis-inducing stem cells, one of which they recognised from breast cancer stem cells. The more of these cells featuring those three markers could be traced in the blood, the worse was the prognosis for the patients. Now the researchers intensively investigate whether these three proteins may be used as targets in the context of breast cancer treatment.

The team of Hai-Kun Liu's DKFZ Young Investigators Group likewise researches cancer stem cells. They recently discovered a key molecule of cancer stem cells in the mouse model, which are responsible for the development of malignant brain tumours. When they switched off production of this protein by genetic interference, the cancer stem cells lost their ability for self-renewal and the cancer ridden mice survived for longer. The brain tumours that Liu and his team researched in mice are similar to aggressive glioblastoma in humans. "We assume that blocking the protein can curb also growth of aggressive brain tumours in humans", says Liu. They have already achieved this in the Petri dish with human glioblastoma stem cell lines. So the protein would be a promising target structure for treatment and the wolves could thus possibly not only be exposed, but also combated.