Tumours, how the bacteria that kills neoplastic cells by starving them works

The idea is truly original. Exploiting the ability of a particular bacterium to consume, like a sort of bottomless pit, the nutrients that favour the development of neoplastic cells. By doing so, at least this is the hope arising from laboratory observations, the aim is to starve solid tumours affecting internal organs. All this, going beyond the treatments, already available, that aim to starve the tumour by limiting the blood and nutrient supply through the vessels it builds, i.e. anti-angiogenesis. Paving the way for the laboratory-redesigned bacterium that starves cancerous units, acting from inside the lesion and then expanding almost in concentric circles (albeit still in the world of the invisible), is original research published in ACS Synthetic Biology conducted by experts at the Canadian University of Waterloo (first name Sara Sadr).

The working hypothesis stems from the very characteristics of the germ considered, which is able to replicate in anaerobiosis, i.e. in oxygen-deprived environments, a condition that also occurs in the most central areas of solid tumour lesions, consisting of dead cells. Clostridium sporogenes, commonly found in soil, apart from its ability to produce spores, can only survive in places completely deprived of oxygen. Making 1+1, therefore, its use has been hypothesised. But beware. while it is true that the 'core' of the neoplastic lesion is made up of dead units and therefore without oxygen, as one moves outwards, oxygen becomes present. and this would cause the bacteria exposed to the aerobic environment to die. This is why it was necessary to treat the germs with a kind of targeted gene therapy, inserting til the genetic trait of a bacterium that better tolerates oxygen, so that the bacteria that starve tumour cells can survive more easily and thus extend their range of action. To regulate this function that makes the germ more tolerant to the presence of oxygen, a system was used that naturally takes place in bacteria on the basis of chemical signals. It is called 'quorum sensing' and practically leads to a signal that is affected by the presence of the bacteria. The more these increase, the stronger it becomes. Thus, the gene that protects the bacteria from exposure to oxygen, favouring their survival, is 'switched on' only when necessary.

It has to be said that it is now necessary to assess how much and how the modified bacterium could really be useful, starting from a biological observation that leaves room for hope. And it is still necessary to start with pre-clinical studies, so the research is really in its infancy. But the mechanism of action, with this sort of biological therapy, is certainly fascinating. And it stems from synthetic biology, with fragments that have their own task even after being reconstituted in the engineered bacterium, potentially transformed into a drug (obviously in the final intent). "This is a rather interesting line of scientific research at the moment, evaluating the behaviour of bacteria that insist in the neoplastic microenvironment, in the tumour microenvironment, which is a very attentive and strategic area of what is the evolutionary development of oncological disease,' comments Paolo Tralongo, director of Medical Oncology at Syracuse Hospital and president of Cipomo, the college of primary hospital oncologists. Through a communication mechanism (the aforementioned quorum sensing, which takes into account the density of the cell population), these bacteria can modulate their activity within the tumour'.

The work, in short, proposes a sort of 'counterpoint' to the norm for germs. In general, in fact, bacteria present in the tumour microenvironment can promote angiogenesis, i.e. the development of the vascular bed, and at the same time promote tissue invasion. But beware. 'By modifying these bacteria through engineering pathways, one can have reflections that are quite interesting, both in terms of therapeutic management and in terms of reducing toxicity,' Tralongo resumes. 'Obviously, this is still a speculative activity that deserves to be reported in a clinical evaluation capable of demonstrating the relationship between the biological idea and the reality of the results in the patient: an interesting idea, but one that must be verified when it is brought to the ground in the clinical setting'. The story, with a kind of scientific 'moral' and wishful thinking, ends with a statement by the Canadian scientists themselves imagining what might happen. The wish is significant. 'Bacterial spores enter the tumour, finding a nutrient-rich, oxygen-free environment, which this organism prefers, and then it starts to consume those nutrients and increase in size,' is the comment in a note from one of the scholars, Marc Aucoin. 'So, we are colonising that core space and the bacterium is essentially ridding the body of the tumour. Now, for this to become a reality, it takes much, much research.