Author:

D.J. Theo Wagener

Date of publication: 20 October 2025
Last update: 20 October 2025

 

The introduction of anticancer drugs also known as cancer chemotherapy in the 1950s and 1960s resulted in the development of curative and palliative treatments for almost all solid tumors and malignant blood diseases. However, the problem with this method of treatment is that this treatment does not work alone on the cancer cells but on all kinds of cells therefore giving all kind of side effects. But because it was the only way of treatment for cancer for more than 70 years and is still in use, we start this overview first to discuss this kind of treatment.

During the past decades a different kind of drugs have become available for the treatment of cancer called targeted therapy. This therapy involves the use of a new generation small molecules and of monoclonal antibodies that have been logically designed to block specific transcription and signal transduction pathways that are essential for the growth and survival of cancer cells. This kind of treatment has theoretically the advantage that it only works on the tumor cells and not on other cells in the body. The drugs consisting of monoclonal antibodies have all ‘mob’ at the end of the name and small molecules ‘tinib’. Although the contribution of scientists of Europe on targeted therapy 3in the last decade is limited, the basis for this therapy is laid by European researchers. A person who should be mentioned anyway in the history of targeted therapy is Paul Ehrlich (1854-1915). He was a German Nobel laureate in 1900. He developed a scientific concept about the magic bullet. While working at the Institute of Experimental Therapy in Frankfurt am Main, Ehrlich formed an idea that it could be possible to kill specific microbes, such as bacteria, without harming the body itself. He named, the hypothetical agent Zauberkugel, the magic bullet. This ‘magic bullet’ of Ehrlich seems at last to be in sight with targeted therapy.

This therapy became possible because the puzzle of the precise structure of DNA was finally solved in 1953 by four British scientists. It was James Dewey Watson (1928-) and Francis Compton Crick (1916-2004), working in Cambridge, who used mainly a molecular modeling approach together with Wilkins using mostly X-ray crystallography technique received the Nobel Prize for this discovery in 1962. Sadly, Rosalind Franklin also working on x-ray crystallography had died of ovarian cancer before that in 1958, at the very early age of 37. Later, it became clear that mistakes in DNA for the most part of tumors are the cause of cancer. That a treatment with monoclonal antibodies can be used for the treatment of cancer goes back to Georges J.F. Köhler from the Basel Institute for Immunology and César Milstein from Cambridge developed the hybridoma technique in the 1970s on principles laid down by Niels Jerner (director of the Basel Institute for Immunology from 1969 until his retirement in 1980) that it became feasible to produce antibodies in sufficient quantities to make effective treatment possible. In the hybridoma technique, a mouse myeloma cell line is fused with mouse spleen cells to produce a clone that is ‘immortal’ (that can grow indefinitely in tissue culture) thanks to the properties of the myeloma cell line, while the spleen cells allow it to produce the desired specific type of antibody. These antibodies which can be produced in very large numbers and with identical properties, are called monoclonal antibodies. Jerne, Köhler and Milstein shared the Nobel Prize in Physiology or Medicine in 1984 for this discovery (Grillo-lópez 2000).

The first theoretical description of antibodies was given by Paul Ehrlich. His side chain theory of antibody formation, developed at the end of the nineteenth century, was the first theoretical explanation of the mode of action of what are currently called antibodies. This hybridoma technique has been used to produce a range of antibodies that influence the growth of tumors, such as trastuzumab, cetuximab, rituximab and bevacizumab. (Wagener, 2010).

Targeted therapy can also be based on much smaller molecules than monoclonal antibodies. The first drug in this class to be discovered was imatinib. (See further) Thereafter came other small drugs available. They have the advantage that also brain metastases can be successfully treated.

References

Burchenal JH, From wild fowl to stalking horses: alchemy in chemotherapy. Cancer1975; 35:1221-35.

Grillo-López AJ., Rituximab an insider’s historical perspective. Semen Oncol 2000; 27) suppl 12) 9-16.

Wagener DJ Th., The history of oncology. 2009. Editor Springer.