Researchers of the Max Delbrück Center (MDC) in Berlin-Buch have now elucidated the key factors for the aggressiveness of this subtype and at the same time have identified targets for the development of new and more effective treatments.
The study by Dr. Jane Holland, Professor Walter Birchmeier, Dr. Balász Györffy (Charité Berlin, Semmelweis University in Budapest, Hungary) as well as Dr. Klaus Eckert (EPO Experimental Pharmacology and Oncology GmbH) has now been published online in the open access journal Cell Reports*.
In contrast to estrogen-positive breast cancer, basal breast cancer is not controlled by this female sex hormone. This cancer subtype lacks hormone receptors, which is why in contrast to estrogen-positive or progesterone-positive breast cancer a “hormone withdrawal” (anti-hormone therapy) has no effect. Progesterone is also a female sex hormone. In the latter form of breast cancer, doctors can suppress the cancer growth with anti-hormone therapies, since drugs block the receptors for estrogen or progesterone on the surface of the cancer cells. Furthermore, breast cancer with receptors for the growth factor Her2 (abbreviation for human epidermal growth factor receptor 2) can be targeted with an antibody which occupies the receptors for Her2.
These therapies are not possible with the basal breast cancer subtype, according to Professor Birchmeier and Dr. Holland. In most cases (about 70 percent), the subtype neither has receptors for estrogen nor for progesterone nor Her2; it is therefore “triple negative”. “Thus, the only possible treatment for this cancer is chemotherapy,” they said. “However, because it is so difficult to treat, researchers and clinicians are seeking new ways to more specifically combat this fast-growing and aggressive type of cancer.An infamous “triple combination”
In addition, a growth factor is involved which researchers have named after its discovery site in the liver: hepatocyte growth factor/scatter factor (HGF/SF). It is referred to as scatter factor because it can separate cells from their respective cluster. It is therefore important for cancer research, as Professor Walter Birchmeier and his staff were able to demonstrate repeatedly: HGF/SF binds to its receptor (Met) in the cancer cell membrane, thus stimulating cancer growth.
In vitro and in vivo in mice, the researchers in Berlin-Buch tested the various inhibitors that have already undergone clinical trials against other cancers but have not been approved. They proceeded step by step, until they ultimately used combinations of the various inhibitors at all three points of attack. Thus, they succeeded in dramatically suppressing cancer growth in mice. Dr. Holland and Professor Birchmeier explained: “A triple attack that blocks both the chemokine system and the two signaling pathways Wnt/beta-catenin and HGF/Met is the most effective.” Dr. Holland added: “This is shown by the fact that after their breast cancer treatment, the mice again formed normal, so-called alveolar structures instead of tumor tissue.” The researchers now hope that their findings will be used in further preclinical trials, and if successful, will also be applied in clinical research.
* Combined Wnt/-catenin, Met and CXCL12/CXCR4 Signals Characterize Basal Breast Cancer and Predicts Disease Outcome
Jane D. Holland1*, Balázs Győrffy2,3, Regina Vogel1, Klaus Eckert4, Giovanni Valenti1, Liang Fang1, Philipp Lohneis3, Sefer Elezkurtaj3, Ulrike Ziebold1, and Walter Birchmeier11 Department of Cancer Research, Max Delbrück Center for Molecular Medicine (MDC), Robert-Roessle-Str. 10, Berlin, Germany
Barbara Bachtler | Max-Delbrück-Centrum
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences