The Australian cancer researcher Dr. Jane Holland of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch was honored on the evening of December 10, 2014 with the Curt Meyer Memorial Prize. She received the prize, which is endowed with 10,000 euros, for her study on basal breast cancer, a particularly aggressive form of breast cancer, which was published online in the open access journal Cell Reports*. The study elucidated the main driver for the aggressiveness of this cancer subtype and at the same time identified targets for the development of new and more effective treatments. The prize was awarded to Dr. Holland, who is thirty-four years old and is originally from Adelaide, Australia, at a symposium in Berlin. Since 2007, she has been a member of the research group led by Professor Walter Birchmeier at the MDC.
Breast cancer is the most common cancer in women. The subtype basal breast cancer, also called estrogen receptor (ER)-negative breast cancer, is particularly aggressive. In contrast to estrogen-positive or progesterone-positive breast cancer, basal breast cancer is not controlled by these female sex hormones. 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. In these types of breast cancer, doctors can suppress the cancer growth with anti-hormone therapies because the drugs block the receptors for estrogen or progesterone on the surface of cancer cells. Furthermore, breast cancer with receptors for the growth factor Her2 can be targeted with an antibody that occupies the Her2 receptors.
These therapies are not possible with the basal breast cancer subtype. In most cases the subtype neither has receptors for estrogen nor for progesterone nor Her2; it is therefore “triple negative”. The only possible treatment is chemotherapy, which is why this cancer subtype is so difficult to treat.
Infamous “triple combination” – triple attack
Dr. Holland showed that an infamous “triple combination” is to blame for basal breast cancer growth. It is comprised of the two signaling pathways Wnt/beta-catenin and HGF/SF, which promote cancer cell growth, plus a system of signaling proteins (chemokines), which activate these signaling pathways. Jane Holland studied this chemokine system during her doctoral thesis at the University of Adelaide in Australia. Mice in which additionally the gene for the receptor CXCR4 of this chemokine system has been inactivated are immune to this cancer subtype.
In vitro and in vivo in mice, the researchers in Berlin-Buch tested various inhibitors that have already undergone clinical trials against other types of cancer but have not yet been used to treat breast cancer and also have not been approved. Ultimately, using combinations of various inhibitors, they were able to target all three attack points and succeeded in dramatically suppressing cancer growth in mice. Dr. Holland and Prof. 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.” Therefore, Dr. Jane Holland together with clinicians from the Charité – Universitätsmedizin Berlin wants to test these inhibitors in human breast cancer tissue in the laboratory.
Since 1988, the Curt Meyer Memorial Prize has been awarded by the Berlin Cancer Society to young scientists working in Berlin for “exceptionally outstanding” publications in the field of clinical, experimental and translational oncology. Prize recipients from the MDC and Charité in previous years were Dr. Dr. Sandrine Sander (MDC, 2013), the biologist Hua Jing (MDC) and the physician Dr. Julia Kase (Charité, 2012), the cancer researchers and clinicians Dr. Martin Janz and Dr. Stephan Mathas (MDC and Charité, 2008), Professor Clemens A. Schmitt (Charité, MDC Guest Group, 2006) and Professor Peter Daniel (MDC/Charité, 2000).
The prize is named after Dr. Curt Meyer, a physician and health official of the Berlin Senate who was born in Herleshausen/Thuringia in 1891. In 1944, he was deported to Auschwitz where he as prisoner took care of fellow detainees suffering from epidemic disease. He survived the concentration camp and after the war dedicated himself to public health, including the care of cancer patients. He was the co-founder of several medical societies, including the Berlin State Committee against Cancer out of which the Berlin Cancer Society has evolved. Curt Meyer died in 1984 at the age of 93.
* Combined Wnt/b-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 Birchmeier1
1 Department of Cancer Research, Max Delbrück Center for Molecular Medicine (MDC), Robert-Roessle-Str. 10, Berlin, Germany
2 Research Laboratory of Pediatrics and Nephrology, Hungarian Academy of Sciences - Semmelweis University, Bókay u. 53-54, Budapest, Hungary
3 Institute for Pathology, Charité Medical University, Charitéplatz 1, Berlin, Germany
4 Experimental Pharmacology & Oncology (EPO), Robert-Roessle-Str. 10, Berlin, Germany
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
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