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The number of new cancer diagnoses has been rising steadily for years. According to estimates by the World Health Organization’s International Agency for Research on Cancer (IARC), the cancer incidence in people aged from 0 to 90 years worldwide was 19.3 million in 2020.1 This incidence is predicted to increase by another 10 million up to around 30.2 million new cancer diagnoses worldwide in the next 20 years.2 Cancer is also still one of the most common causes of death worldwide. In 2020 alone, an estimated 9.9 million people worldwide died from cancer.3
The growing incidence of cancer is mainly due to our ageing society, as age is an independent risk factor for the development of cancer. At the same time, the possibilities for the early detection of cancer are developing, e.g. through growing implementation and comprehensive use of preventive cancer screening programmes worldwide.
Another component in future early detection of cancer is the increase in development of new molecular methods (e.g. “liquid biopsies”), designed to detect circulating cancer cells in human body fluids. Multicancer detection tests are being tested in population trials to check their potential as future new cancer screening methods. It is likely that new molecular methods for detection of early cancer will also have an impact on the figures of cancer incidence in the future.
The predicted increasing cancer incidence and the still very poor prognosis of certain types of cancer, e.g. malignant brain, pancreatic or blood cancers, are posing a challenge to researchers in cancer medicine who are pursuing the goal of developing ever more effective therapies.
For decades, cancer medicine focused on the direct removal of malignant tumours or the destruction of cancer cells. The most important pillars of cancer therapy are the oncological surgical resection of tumours, chemotherapy and radiological radiation. Surgical procedures and treatment protocols have been continuously developed and they remain effective cornerstones of cancer treatment to this day.
The usual goal of classical cancer therapy is the complete removal of a malignant tumour. When the tumour is resected, a margin around the tumour is maintained and, as a rule, the associated lymphatic drainage area of the resected organ or organ part is also removed (oncological resection). Tumour resection and lymph node removal serve to minimise the risk of tumour recurrence and thus improve the survival prognosis. Chemotherapy and radiotherapy after (adjuvant) or before (neoadjuvant) surgery also serve to reduce the risk of a recurrence by destroying potentially remaining cancer cells.
In recent years, various new therapeutic measures have been added to the tried and tested forms of therapy. A new era in cancer research and treatment began early in the 21st century: the era of immunotherapy. Immunotherapies are, in the broadest sense, substances that support the immune system in its response to various external threats, such as cancer cells.
Initially, researchers studied cancer cells and their specific characteristic features. An important step in this context was the introduction of so-called “biomarker testing”. Biomarkers are biological characteristics that can be measured and assessed in blood or tissue samples – including cancer cells.
Changes in the expression or quantity of certain genes can now be determined molecularly and provide information about the specific characteristics of a cancer. Cancer cells sometimes show very typical characteristics on their surface, called “tumour-specific” or “tumour-associated” antigens. These are found either not at all or only in a different form or frequency on healthy body cells.
Based on these cancer-typical characteristics, targeted therapies can be developed to eliminate cancer cells more effectively. The research focus lies primarily on specific characteristics favouring cancer cell proliferation and spread in the human body. By targeting these characteristics with specifically tailored drugs, many types of cancer can be inhibited in their growth more effectively.
Testing cancer tissue for specific biomarkers also has the advantage of sparing patients from ineffective or less effective therapies in the absence of these biomarkers.
In 1997 and 1998 respectively, the first targeted immunotherapies in the form of monoclonal antibody therapies were approved: rituximab for patients with previously treatment-resistant B-cell non-Hodgkin’s lymphoma, and trastuzumab for the treatment of HER2-positive breast cancer.4
Cancer research today is not focusing only on the field on specific features of cancer cells, but also on how the human immune system with its different cell types and messenger substances acts against cancer cells. Intensive research of the detailed processes of the human immune system’s response to cancer is contributing to the development of further immunotherapies.
The aim of these types of immunotherapies is essentially to support and strengthen the human immune system in its fight against cancer cells. Various immunological approaches are now available.
Antibodies recognise target structures (antigens) on other cells and can eliminate them directly, e.g. by interfering with the growth of these cells. They are produced by the human immune system against specific antigens. By applying lab-produced, targeted monoclonal antibodies, the body’s own immune system is supplied with artificial immune cells that react to corresponding cancer antigens.
These modified antibodies attach to cancer cells, provoking a stronger immune reaction. Processes that are essential for the growth and metabolism of cancer cells are specifically disrupted. Today, many different substances matching to different types of cancer specific-antigens are available. Accordingly, they can be used to treat many different types of cancer.5
Immune checkpoint inhibitors are another type of antibody therapy. They are not directly directed against cancer-specific features, but against the immune system’s own control mechanisms, the so-called “immune checkpoints”. The task of these immune checkpoints in the human body is to prevent excessive immune responses by the immune system in order to protect healthy cells.
Cancer cells are able to activate these checkpoints to a great extent and thus slow down the immune response against them. By specifically switching off the checkpoints, the suppression of the immune response by cancer cells is lifted and the path is cleared for a strong immune response.6 Checkpoint inhibitors have been approved for various types of cancer. The research in this method was recognised in the awarding of the 2018 Nobel prize in Medicine.
The principle of this form of treatment lies in the modification of the body’s own immune cells, the T cells. It is an individual therapy in which the patient’s own T cells are taken and genetically modified in the laboratory. The modification causes the T cells to form proteins on their surface, known as CARs (chimeric antigen receptors). These in turn recognise and bind specific antigens that are present on the surface of certain cancer cells.
After the genetically modified T cells have been multiplied in the lab, they are administered to the patient to achieve a stronger immune response against cancer cells. CAR T-cell therapies are approved for the treatment of various forms of blood cancer, such as lymphoma, some forms of leukaemia and, more recently, multiple myeloma.7
Cytokines are natural messengers that guide communication between immune cells. Among other roles, they stimulate cell proliferation and the development of different cells of the immune system. Cytokines as immunotherapies were introduced years ago and were initially regarded as a great hope in modern cancer therapy. However, this hope could not be fulfilled.
Primary cytokines, such as interferons, interleukins and colony-stimulating growth factors, showed no significant therapeutic effects in various studies, but caused frequent, severe side-effects instead. However, studies have shown their positive effects in combination with other immunotherapies, the form in which they are administered today.8
Oncolytic viruses are regarded as one of the biggest breakthroughs among therapies boosting the body’s own immune response. An oncolytic virus is a genetically modified virus that infects cancer cells but leaves normal cells unharmed. The virus multiplies specifically in cancer cells and leads to their destruction (oncolysis). The destruction leads to the release of cancer tumour antigens, which additionally activates the immune system. This enables a better recognition and response to cancer cells.
Approved since 2015, genetically modified forms of the herpes virus have already showed clinical benefits in patients with advanced melanoma. Other applicable cancers include ovarian cancer, cervical cancer and certain malignant brain tumours.9
This is not a vaccination to protect against cancer-promoting viruses, as in HPV vaccination, but a targeted vaccination of patients who already have cancer. Cancer patients are vaccinated with cancer antigens in a high dosage, characteristic of the underlying malignancy. The aim is to support the immune system to react strongly to the antigens and to produce more antibodies.
For this purpose, the individual’s own immune cells are collected and then molecularly modified or loaded with antigens. The modified immune cells are multiplied in the lab and returned to the patient. The mRNA-based method is not yet a standard method in cancer treatment, but it is already being applied in current clinical studies.10
Cancer cells have the ability to create an environment for themselves that suppresses the immune system and promotes their own spread. In this microenvironment, immunogenic reactions to the cancer cell are prevented and its spread is supported by the formation of new blood vessels and metastases.
Altering this microenvironment could be the key to controlling tumour immunity and tumour growth in the future. The administration of modified ribonucleic acid interference (RNAi) nanomaterials is a promising new method for regulating immune responses and restoring tumour-destroying mechanisms.
It implies the modification of genes in which the formation of the cancer cell’s target gene is inhibited by synthetic gene components. Modified RNAi particles are applied organ-dependently to reach the target tissue and consequently interact with the local immune and tumour cells.
Corresponding studies on treatment trials with these immune system modulators could provide the entire scientific community with fundamental insights into gene therapy and prove revolutionary for the treatment of cancer.11
Surgery, chemotherapy, radiotherapy and targeted therapies directly aim to remove or destroy cancer cells. Immunotherapies are changing the effectiveness of immune cells and represent a rapidly evolving paradigm in current cancer research. The approach of treating cancer by boosting the immune system is on the rise and already in use for cancer patients. Multiple studies have already demonstrated the efficacy of immunotherapies against different types of cancer. Not every cancer patient can be helped satisfactorily, however. The question of why certain cancer therapies work for one patient but have less or no effect for others is a major question that continues to concern scientists.
There is still much room for further development through more and new insights into the functioning of the human immune system in its interaction with different types of cancer cells. In the future, new insights will enable researchers to develop new immunotherapies, and to test synergistic combination treatments that could bring long-term benefits to more patients in the future.
Despite a growing incidence of cancer diagnoses in the upcoming years, the possibility to bend the current cancer mortality rate curve is quite high. It can also be assumed that this development will continue to have a positive impact on the development of extra premiums in life insurance. The insurance industry should always keep pace with new developments in cancer treatment, the upcoming new methods of early cancer detection and the impact of both on cancer mortality rates.
All endnotes last accessed on 15 November 2023.
