Overview of cancer therapies

Historical review

Surgery and medicine

Surgery, which for a long time was a discipline independent of medicine, was initially the main approach to cancer therapy.

Drugs as defined in pharmacologic terms became available only a century ago. Based on the accomplishments of pharmaceutical chemistry, the drug industry skyrocketed by the mid 20th century.

Many of the most potent drugs originate in the natural environment. Probably the most prominent drug of this class is penicillin; but also substances like digitalis and taxanes are derived from nature. The first taxanes, powerful cytotoxic drugs for the treatment of breast cancer, were derived from the pacific yew.

Mustard gas: trigger for the development of cytotoxic chemotherapy

The systematic development of cytotoxic chemotherapy started in the mid 20th century. Soldiers exposed to mustard gas during the two world wars were observed to have greatly reduced white blood cells that only hesitantly recovered. This effect was thought to be useful for the treatment of leukaemia. It took several years of intense biomedical research and the dedication of many leukaemia patients to replace the much too poisonous mustard gas with substances that had acceptable adverse effects but still were capable of destroying leukaemia cells.

Irradiation

Marie Curie discovered radioactivity at the turn of the 19th century and was awarded a Nobel price for her work in 1911. Soon after that discovery, biomedical scientists started to use the destructive capacity of radioactive rays for cancer treatment. However, only the invention of linear particle accelerators in the mid 20th century permitted the systematic use of radiotherapy.

Surgery and radiotherapy are established and undisputed pillars of cancer treatment. During the last years, considerable advances were made in the field of drug based cancer therapy. Many of the novel drugs target molecules critical for cell division and survival. These concepts were designated Targeted Therapies. They hold potential for an effective cancer treatment with a lower number of severe adverse events as compared to older cytotoxic drugs.

First experiments using cancer immune therapy

The idea of using the immune system‘s capacity to destroy cells gained momentum towards the end of the 19th century. In 1893, the New York physician William B. Coley first reported on his cancer immune therapy experiments. He had injected heat-inactivated bacteria into the tumour tissue. The resulting abscess caused considerable collateral damage that destroyed tumour tissue. By the name of Coley’s toxin, this concept remained a treatment option for a long time as a complement to surgery.

Even today, this treatment is applied in a basically identical form. Inoculation of the tuberculosis vaccine BCG (Bacillus Calmette-Guérin), a weakened form of the causal agent of tuberculosis, into the tumour tissue is a standard therapy for bladder cancer.

The fourth pillar of cancer treatment

The classical treatment options for cancer are surgery, irradiation, and chemotherapy. Cancer immune therapy has the potential to become the fourth pillar of cancer treatment. In 2010, the first cancer immune therapy based on dendritic cells was approved for the treatment of advanced prostate cancer.

Cancer immune therapy

The primary objective of cancer immune therapy is to enable the immune system to gain control of neoplastic diseases.

The concepts of cancer immune therapy are almost as manifold and complex as the immune system itself. There are technologies based on T-cells or methods that apply synthetic or recombinant tumour antigens to cancer patients in the context of adjuvants. The tumour antigens may be loaded onto dendritic cells, they may be introduced into a viral genome using genetic engineering and they could be comprised of autologous or allogeneic tumour cells with or without various genetic engineering to enhance their immunogenicity.

Cancer immune therapy is usually applied as an add-on to the standard first line cancer therapy. The ultimate goal is to establish cancer immune therapy as a stand-alone concept in the oncologists’ arsenal for combating cancer.

The ideal domain of cancer immune therapy will be the so-called adjuvant cancer treatment. Typically, this is a drug treatment which is given as a safety measure. It is applied in cases where a tumour was surgically removed, but it is not absolutely certain that no tumour tissue remains. From this remaining tissue, a relapse might originate. The advantage of cancer immune therapy in an adjuvant setting is that in light of current knowledge only minor adverse events are expected. In contrast, using cytotoxic drugs in adjuvant chemotherapy is expected to frequently cause considerable side effects.