What are the starting points for therapy?

Tumours tend to spread out and transform metabolic pathways in a very individual way for their own purposes of increased energy production and improved cellular communication. They do this by switching on and off of certain genes containing the construction plans and working instructions for the respective metabolic pathways in the genome according to their requirements. The primary tumour and healthy cells thus differ greatly in the activity of certain genes. With this, however, the tumours also create their own Achilles heel, where medicaments can attack effectively once these points of action have been recognized and defined.

Points of action:
i) Because of their rapid growth, tumour cells require improved communication links; they need a kind of highly efficient telephone network. At a cellular level this communication takes place via chemical substances such as hormones, peptides, ions (calcium, sodium etc.) and proteins. As in a normal telephone network the tumour also maintains receiver stations and intersections, which at a cellular level are known as receptors and neural nodes. These receptors and intersections are increasingly formed and used in an individual way by tumours.

This broadcasting network should be elucidated and inhibited.

An example is the EGF receptor which is located on the surface of the cell and passes signals from neighbouring cells to the cell nucleus, or vice versa also acts as a transmitter station. Biochemical analysis can ascertain whether there has been an increased formation of the EGF receptor (or increased expression, as molecular biologists would say) by the tumour switching on a certain gene. If this is the case, the EGF receptor can be blocked by appropriate drugs and the tumour’s signal chain is disabled.

Another example is the ERBB2 receptor located in breast tumours. Investigations have shown, however, that this is only the case in approx. 30% of the tumours. It therefore makes sense to test whether there is an expression of the ERBB2 receptor in the patient`s tumour or not. If this investigation is not performed and there is no expression of the ERBB2 receptor in the tumour, the would-be therapy is absolutely ineffective and just causes only considerable side effects.

ii) Sophisticated new generation drugs only become active through certain enzymes that are produced in larger amounts by the tumour for its own purposes. These are also known as “prodrugs“. The prodrug gemcitabine requires the enzyme DCK to change into its active form. This enzyme is over-expressed by some tumours. In other words, the tumour supplies the tool for its own destruction. However, if the enzyme is not produced in increased amounts in the tumour cells the therapy has no effect.

iii) Other drugs disable certain enzymes that the tumour cell needs for its rapid growth. Examples are the topoisomerases which are required for cell division. Tumours have a much higher rate of cell division than healthy cells, and produce larger amounts of e.g. topoisomerase I. This fact can now be utilised therapeutically. If the analysis shows that the topoisomerase I is highly expressed in the tumour, the enzyme can be blocked by means of drugs, e.g. irinotecan, with the result that the tumour is deprived of one of its essential tools.

iv) Healthy cells have developed techniques to get rid of substances which could be harmful. The cells produce specialised proteins which transport harmful substances, but also certain medicaments, very effectively out of the cell. Some tumours copy this system for their protection: they produce an increased amount of transport proteins and certain drugs then have little or no effect.