Nearly four decades ago the former US President Richard Nixon declared war on cancer – since then, physicians know that the fight is longsome and hard. But the arsenal of the oncologists has changed. A whole palette of agents gradually led to an upheaval in cancer medicine.
Because – compared to the previously used drugs which as classical cytostatics attacked both, healthy and tumor cells equally without reacting to the molecular details in tumor cells just two decades ago – the drugs in 2008 intervene in important pathways, biochemical signal ways of tumor development. Whoever as a physician knows the mode of action and exact mechanisms of the preparations is able – by encroachment on specific targets – to prolong the life of his patients considerably.
A complex endeavor
Already the list of the top ten active ingredients, recently published by the British economic magazine New Scientist, unveils that the trouble in dealing with the armada of tumor combatants starts with the name of the preparation. Sounds fanciful? A self test reveals that it’s not. Just by reading the following list, every physician will realize, how at the end of those lines, the names of the active ingredients start melting into a nebulous nirvana: Bevacizumab, Sorafenib, Imatinib, Tamoxifen, Bortezomib, Gefitinib, Rituximab, Everolimus, Trastuzumab, Tositumomab.
But what exactly do those preparations bring about? And what do you have to keep in mind when applying them? First of all you need to know what you are getting yourself into. For example Bevacizumab. This active ingredient belongs to the class of antibodies and targets the so-called VEFG growth factor. Unwelcome effect: This way the tumor provides for the structure of blood feed supply ways. But the active ingredient is primarily suitable for use in patients with collateral cancer, just as for fighting against non-small celled lung cancer. Under certain conditions breast cancer patients react to the preparation as well. By using this active ingredient, physicians are able to curb the angiogenesis of tumor cells by exactly aiming at a target – but this works only for the above mentioned tumor types.
Sorafenib aims at two molecular targets likewise: VEGFR and PDGFR. Here as well, the angiogenesis is being curbed but the substance does even more. In addition to the growth factor it attacks the so-called c-kit receptor as well and it docks on to certain protein kinases. This therapy is suitable for patients with kidney- and liver cancer.
Signal ways and plenty of traps
The example of Imatinib demonstrates particularly impressively just how tricky and full of traps an encroachment on the signal ways can get. This active ingredient attacks the enzyme BCR-ABL appearing if a patients has leukaemia or gastroenterological tumors. But: Mutations of the cancer cells can create resistances against the preparation. A physician should know those details. Whoever does not know will loose valuable time – time he might need to side step and use other active ingredients.
But today exactly this is considered the elementary precondition for a successful therapy. The example of breast cancer reveals it. Here physicians have in addition to Tamoxifen the active ingredients Trastuzumab or likewise Bevacizumab available – to name just a few. Just for this one type of cancer, the palette seems extensive but: What should be used? At any rate Tamoxifen should not be applied if the patients do not have a certain type of estrogenic receptors in the tumor cells because the active ingredient does not work at all without this molecular target – a truism many practicioners are not familiar with.
Even the concentration of the targets in the organism of the patients determines over their life or death. For example Trastuzumab does only work successfully if the drug molecules find the HER2 receptor in adequate quantities. But that is only the case in about 25 percent of all breast cancer patients –due to their genetic disposition all the others are not at all able to bring up the target molecules.
The problem: The costs for treatment
Particularly tricky cancer physicians are able to work against non-small celled lung cancer because in addition to Bevacizumab the physicians avail over Gefitinib, an active ingredient effective only on special mutations of the tumor cells. After all 15 percent of all patients within this cancer category can be treated with this therapy – provided that the mutation of the surface protein EGFR was discovered.
Lymphomae again require a completely different active ingredient therapy. Rituximab und Tositumomab are considered especially promising. Both attack the surface protein CD 20 found on the B-cells of the organism. But in the end, the limiting reasons as often cannot be a potential medical success of a therapy but the take-over of costs by the health insurances. At least in the US, cancer physicians are facing a massive problem with Tositumomab: A single treatment costs 27,000 US-Dollars.