Cookie Settings

We use cookies to optimize our website. These include cookies that are necessary for the operation of the site, as well as those that are only used for anonymous statistic. You can decide for yourself which categories you want to allow. Further information can be found in our data privacy protection .


These cookies are necessary to run the core functionalities of this website and cannot be disabled.

Name Webedition CMS
Purpose This cookie is required by the CMS (Content Management System) Webedition for the system to function correctly. Typically, this cookie is deleted when the browser is closed.
Name econda
Purpose Session cookie emos_jcsid for the web analysis software econda. This runs in the “anonymized measurement” mode. There is no personal reference. As soon as the user leaves the site, tracking is ended and all data in the browser are automatically deleted.

These cookies help us understand how visitors interact with our website by collecting and analyzing information anonymously. Depending on the tool, one or more cookies are set by the provider.

Name econda
Purpose Statistics
External media

Content from external media platforms is blocked by default. If cookies from external media are accepted, access to this content no longer requires manual consent.

Name YouTube
Purpose Show YouTube content
Name Twitter
Purpose activate Twitter Feeds

Breast cancer: altered chromosomes lead to treatment resistance

No. 10 | 26/02/2020 | by Rei

If chromosomes are unevenly distributed or otherwise altered during cell division, this normally damages the daughter cells and impairs their viability. Not in cancer cells, however, in which chromosome instability can actually confer a growth advantage under certain circumstances. Moreover, as scientists from the German Cancer Research Center have now demonstrated in mice, changes in the chromosomes can lead to breast cancer cells becoming resistant to treatment. The researchers have thus gained new insight into the mechanisms by which tumor cells circumvent the effect of treatment.

Unstable chromosomes can promote breast cancer
© Adobe Stock

In cell division, the chromosomes of the parent cell are normally divided equally between the two daughter cells. Errors in the structure or number of chromosomes during this process are referred to as chromosome instability. The consequences for the affected cells are severe: The wrong amounts of proteins are produced, the metabolism gets out of control, and the cells often eventually die by programmed cell death (apoptosis).

The situation is different in cancer cells. The abnormal number of chromosomes appears to provide a survival advantage. Chromosome instability is regarded as an indicator of an unfavorable course of disease in cancer and is also thought to be associated with treatment resistance. The mechanisms underlying this survival advantage were not previously clear, however.

"In fact, 90 percent of solid tumors and 75 percent of hematopoietic tumors have unevenly distributed chromosomes," explained Rocio Sotillo from the German Cancer Research Center (DKFZ). It is not necessarily whole chromosomes that are unevenly distributed. Segments of chromosomes can also get lost or be replicated.

Sotillo and her team have now demonstrated that chromosome instability itself can contribute to treatment resistance. To do so, the researchers resorted to various tricks in the field of molecular biology and bred mice in which the cancer-promoting gene KRAS can be specifically switched on – these animals thus develop breast cancer. In a second group of mice, the researchers activated another gene alongside KRAS, hence causing very pronounced chromosome instability.

In the next step, the DKFZ scientists switched off these genes again, which in principle simulates the effect of targeted treatment. In theory, cancer growth ought to have stopped in both groups. However, in more than 20 percent of the animals with chromosome instability, the tumors continued to grow – as they did in 6.6 percent of the mice in which only KRAS had previously been activated and chromosome instability had not been induced.

Moreover, when the researchers continued to observe the tumor growth, they discovered that the tumors in which the chromosomes had not been made unstable using the genetic trick showed anomalies too. The error rate in cell division was in fact just as high as in the animals in which chromosome instability had been induced right from the start.

More detailed genetic analysis of the resistant tumors showed that in half of the mice affected, certain chromosome segments had been replicated. During this process, an oncogene that is known to confer treatment resistance on many tumors was also replicated. The scientists treated the animals using a substance that targets the signaling protein for which this oncogene codes, and all the tumors did indeed reduce in size.

"The trick involving activating and then turning off genes allowed us to simulate targeted cancer treatment. Chromosome instability acts as a driver of genetic variability that confers a survival advantage through resistance development on the cancer cells under the treatment-related selection pressure," explained Sotillo, summarizing the results. "A few originally chromosomally stable tumor cells survive the treatment by acquiring chromosome instability at the same time. This increases their chances of developing treatment resistance."

The researchers still do not know what mechanisms of molecular biology underlie this effect and intend to devote future research to this issue. "We hope this will help us understand better how chromosome instability arises and hence resistance develops during targeted cancer treatment – and how we might be able to prevent it," Sotillo remarked.

Lorena Salgueiro, Christopher Buccitelli, Konstantina Rowald, Kalman Somogyi, Sridhar Kandala, Jan O. Korbel and Rocio Sotillo
Acquisition of chromosome instability is a mechanism to evade oncogene addiction.
EMBO Mol. Med. 2020, DOI: 10.15252/emmm.201910941

With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.

To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:

  • National Center for Tumor Diseases (NCT, 6 sites)
  • German Cancer Consortium (DKTK, 8 sites)
  • Hopp Children's Cancer Center (KiTZ) Heidelberg
  • Helmholtz Institute for Translational Oncology (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ
  • DKFZ-Hector Cancer Institute at the University Medical Center Mannheim
  • National Cancer Prevention Center (jointly with German Cancer Aid)
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.


Subscribe to our RSS-Feed.

to top
powered by webEdition CMS