The goal of oncology research at Bayer is to improve the lives of people affected by cancer.
A key starting point is the identification of suitable molecular targets at different stages of tumor evolution from which novel therapeutic strategies can be derived.
Tumor metabolism and hypoxia
In the 1920s, Otto Warburg observed that tumor cells consume a large amount of glucose, much more than normal cells, and convert most of it to lactic acid. This phenomenon, now known as the Warburg effect, is the foundation of one of the earliest general concepts of cancer, i.e. that a fundamental disturbance of cellular metabolic activity is at the root of tumor formation and growth.
Tumor metabolism research focuses on attacking the tumor´s increased demand for important nutrients such as glucose and amino acids.
Tumor growth under oxygen deficiency leads to resistance
Furthermore, as a result of the tumor´s uncontrolled growth, the oxygen supply is significantly lower in some tumor regions than in healthy tissue.
This oxygen deficiency is called hypoxia. Cancer cells that survive in such a hypoxic environment are often resistant to conventional radio- and chemotherapy because of their altered metabolism.
Scientists at Bayer are engaged in research on the resistance mechanisms present in hypoxic, or oxygen-starved, cancer cells.
If these resistance mechanisms can be suppressed, or their impact reduced, cancer cells or tumors that have been therapy-resistant up to now could be specifically targeted and combated, e.g. in combination with such established treatments as radiation therapy.
A cell´s DNA is packaged in the so-called chromatin in a complex with histone proteins.
In healthy cells, the access to DNA and therefore the availability of the genetic information is tightly controlled.
Before certain cell mechanisms can access the DNA strand (for example to repair damaged chromosomes or read the genetic code to produce the proteins that are needed), the chromatin must first be modified by controlled biochemical processes.
Disrupted chromatin modification in tumor cells
This chromatin modification is often disrupted in tumor cells: certain DNA segments can then, for example, lie open, permanently unprotected, so that the information stored there can be read at any time and translated into proteins that are important for the uncontrolled proliferation of cancer cells.
Researchers at Bayer are looking for ways of restoring the original chromatin packaging - thereby potentially stopping the uncontrolled growth of cancer cells.
Immunotherapy and antibody-conjugates
The immunotherapy approach combats cancer using the body´s own immune system. Researchers at Bayer are developing specific antibodies that are geared towards the characteristics of cancer cells - they specifically "lure" the body´s immune cells (killer cells) to the tumor, where they are activated.
This enables the immune system to recognize the cancer cell as hostile and destroy it.
Antibodies specifically geared towards the characteristics of cancer cells are also used in the development of what are known as antibody-drug and antibody-thorium conjugates.
The (monoclonal) antibody recognizes or binds to certain protein molecules ("tumor markers") on the surface of the tumor cells by specifically targeting these cancer cells.
Antibody-drug conjugates as Trojan Horses
Antibody-drug conjugates (ADCs) consist of three different components which give the conjugate its typical properties: the (monoclonal) antibody, a cytotoxic active ingredient (the toxophore), and a linker connecting the antibody and toxophore. Once taken up by cancer cells the ADC unloads its cytotoxic "payload", the toxophore, directly inside the tumor cell, and it can then unleash its destructive effect and trigger programmed cell death (apoptosis).
Using radiation against the tumor: Antibody-thorium conjugates
Antibody-thorium conjugates are similar to ADCs. In this case the radioactive alpha emitter thorium-227 is complexed by a chelating linker that is attached to an antibody.
Unlike for ADCs, it is sufficient for the thorium conjugates to be bound to the surface of the tumor cells with no need for uptake into the inside of the cells for efficacy. The thorium conjugates emit alpha particles that result in an effective killing of tumor cells by inducing DNA double-strand breaks.
Cell cycle and survival signaling
In a healthy organism, cell division is subject to a strict control mechanism - errors that occur during cell division are detected and corrected. Cells that are irreparably damaged die off (programmed cell death, also known as apoptosis) without passing on this defect of cell cycle control.
Disrupted cellular control mechanisms in cancer cells
In cancer cells, these and other cellular control mechanisms have ceased to function properly. Unlike healthy cells, cancer cells have a number of activated signaling pathways that enable them to survive and proliferate in an uncontrolled way, thus leading to the development of cancer or tumors. The cause of resistance or cancers being refractory to traditional chemotherapy may also be found here.
Scientists at Bayer are concentrating on stopping the proliferation of cancer cells by interfering with the biochemistry of their cell cycle or survival-signaling pathways. In this context they focus on mechanisms that are important for cancer cells but not as essential for normal cells. Researchers are committed to the discovery of novel targeted agents which block these and other signaling pathways.