Is it ever legal to ship weeds
Weeds have stolen the nerves of many a gardener. Fortunately, there is a relatively simple way to get rid of it: “You can prune the leaves off the weeds again and again, but they will grow back. On the other hand, if you remove the roots, the leaves will also die. " This is the plausible advice from Dr. John Dick from the University of Toronto, who at first glance may seem downright trivial. But John Dick's interest is not in gardening, nor is his comment on weed removal. Instead, it is about something much more useful: How we can get rid of cancer - a disease that we still cannot cure in the vast majority of cases. But what are the correspondences of a plant root in a malignant tumor? There is evidence that it is a group of cells called “tumor stem cells,” and great hopes have been placed in treating cancer by treating these cells therapeutically. Since hope and hype are often closely related, let's take a closer look at the matter.
Slider photo: metastatic breast cancer, Credit: Ed Uthmann (CC BY 2.0)
The cancer stem cell hypothesis states that not all tumor cells have the same abilities, but that each tumor has a small group of cells with stem cell-like abilities that maintain the growth of the tumor, while the bulk of the tumor cells do not have this ability - as in one Hierarchy. These cells are also blamed for relapses that can occur many years after the initial treatment. Indeed, it is believed that common chemotherapies that attack rapidly dividing cells leave the relatively slow dividing tumor stem cells untouched and therefore allow for later relapses. Furthermore, tumor stem cells have been associated with increased radiation resistance, invasiveness and a poorer prognosis. In short, if you can call a cancer cell malignant, then a cancer stem cell is many times more malignant! A common misconception is that a tumor stem cell is a sub-form of normal stem cells and therefore cancer arises from stem cells. That's not the case. The term “tumor stem cell” only reflects the fact that it is a tumor cell with capabilities similar to those of normal stem cells, for example the self-preservation of the cell for an indefinite period of time. Tumor stem cells are often mistaken for the cell of origin of a tumor. The cell of origin differs depending on the type of cancer and does not have to be a tumor stem cell. In some cases, such as certain brain tumors, the cell of origin is not even known.
Scheme of the difference between conventional cancer therapy and cancer stem cell therapy. Image: Public Domain
But how did this research area come about? As early as the 1960s it was discovered that not all cancer cells have the same ability to form tumors. 30 years later, in 1997, the cancer researchers Dominique Bonnet and the aforementioned John Dick reported in Nature Medicine about the leukemia stem cells they had recently discovered, thus establishing a completely new branch of cancer research. The cancer stem cell concept was born, and in the years that followed, such cells were discovered in many other cancers such as breast, brain and prostate cancer. Like any scientific theory, it initially faced a lot of criticism and doubt. A breakthrough came in 2012 when three independent studies were published, all of which confirmed a cellular hierarchy and thus the tumor stem cell concept by using scientifically robust techniques to track individual tumor cells and their progeny. Since then, there have been no more doubts about the existence of cancer stem cells. Much of the research in the field is concerned with finding a so-called marker, i.e. a molecule whose presence on a cell unequivocally identifies it as a cancer stem cell. To date, no reliable molecule has been identified - in one way or another, all the markers proposed and used are highly controversial. Indeed, the marker problem is unlikely to ever be satisfactorily resolved, and it might make more sense to define the definition in terms of functional properties rather than surface molecules, although the latter would of course facilitate targeted therapies. Unfortunately, many studies are based only on experiments in the Petri dish, often not even with primary cells directly from patients (which are more difficult to obtain), but with less representative material from cell lines. On the other hand, the first clinical studies with drugs against cancer stem cells are now being carried out, with moderately positive results so far.
Brain tumor stem cells in a petri dish, so-called “spheroids”. Image: Minu D. Tizabi
Doubts about the existence of cancer stem cells may have been dispelled in 2012, but in fact we are only gradually beginning to understand that the situation may be much more complicated and less clear-cut than originally thought.It was recently found that different tumors of the same type can be based on completely different tumor stem cell populations. As if that didn't make things complicated enough, it has also been found that even one and the same tumor can harbor several different stem cell populations in its center! In addition, it is possible that some cancers may follow the cancer stem cell model while others do not. It is difficult to predict what the future holds for the cancer stem cell field, but it is likely that the three new discoveries mentioned will require a fundamental change in our approach. In summary, it can be said that cancer stem cells have been a major trend in cancer research over the past decade and a half, but the hopes placed in them are based on a solid experimental basis and are therefore entirely justified. Nevertheless, the field is currently struggling - not least due to a lack of standardization of methods - with many problems such as the challenge of developing a clear definition and identification option for tumor stem cells. As with other potential cancer therapies, no one can predict whether the efforts will ultimately pay off clinically - but the chances are that it will, and the research field could even be headed for a Nobel Prize. So let's keep our eyes and ears open for new developments in this exciting field!
Slider photo: metastatic breast cancer, Credit: Ed Uthmann (CC BY 2.0)
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