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New insights into the development of cancer
Cancer is an extremely complex disease. The exact mechanisms that lead to its creation are still unclear in detail. An international research team with the participation of the German Cancer Research Center has now for the first time documented the molecular events that take place when healthy tissue comes into contact with carcinogenic substances.
Researchers from the German Cancer Research Center and the Universities of Cambridge and Edinburgh were able to observe and understand the molecular evolution of tumors in detail for the first time. The team found that damage caused by cancer-promoting substances is passed on to several cell generations, which can result in new differences between the mother and daughter cells. These variations are the basis for the development of cancer cells. The results were recently presented in the renowned "Nature" journal.
Cancer: Exact processes in the development still unknown
Many chemicals or radiation are able to damage our genome and thereby trigger cancer. The most well-known triggering factors include UV radiation from sunlight and tobacco smoke. There are also numerous other environmental influences and chemicals to which our bodies are exposed. Cancer has long been associated with such factors, but the molecular processes involved in the onset of the disease are still poorly understood.
Cancer development in mice analyzed
The international research team has now taken a big step closer to solving this riddle. The researchers exposed mice to the strong liver cancer-causing chemical diethylnitrosamine and thereby analyzed the genetic makeup of the animals. This enabled them to understand step by step how the substance causes the first DNA damage to lead to liver cancer.
This is how cancer develops
The chemical initially caused damage to individual DNA building blocks of healthy cells. These building blocks are called nucleotides. If the damaged cell divides, the information is no longer passed on correctly due to the damage, as a result of which the divided daughter cell is slightly different from the mother cell. According to the researchers, this creates two strands of DNA with different defects.
These cells divide further and further, which means that new errors develop again and again, resulting in a complex pattern of mutations. In the end, there is a very good chance that these mutations will develop into cancer cells that form a tumor. It was surprising for the team that such mutations develop over several cell generations and that the errors are always passed on without the cells repairing the DNA damage.
The strongest mutations survive
"In the end, those cancer cells that carry the cheapest pattern of mutations prevail," emphasizes student author Sarah Aitken from the University of Cambridge. These cells can grow fastest and can also escape the immune system better. Aitken says that fast-growing cancer cells are often more resistant to cancer therapies.
Chemotherapy drugs can trigger mutations
“Certain chemotherapy drugs can also induce DNA damage, which also segregates and creates further mutations over several cell generations,” adds Martin Taylor from the University of Edinburgh. This fact must be taken into account when developing future cancer drugs.
Cancer development more complex than previously thought
"With the concept of damage segregation, we now understand better than before how the astonishing complexity of mutations in cancer cells can arise," adds Duncan Odom from the study team. This also explains why tumors are so extremely adaptable. This adaptability helps cancer cells to develop drug resistance or to settle in foreign tissue. (vb)
Read also: New active ingredient stops tumor growth.
Author and source information
This text corresponds to the requirements of the medical literature, medical guidelines and current studies and has been checked by medical doctors.
Graduate editor (FH) Volker Blasek
- Sarah J. Aitken, Craig J. Anderson, Martin S. Taylor, and others: Pervasive lesion segregation shapes cancer genome evolution; in: Nature, 2020, nature.com
- German Cancer Research Center: New explanation for the extreme complexity of mutations in the tumor genome (published: June 24th, 2020), dkfz.de