Researchers at the Austrian Academy of Sciences’ Institute for Molecular Biotechnology (IMBA) have identified a remarkable connection between sex hormones and primary lung cancer. A medicine that has already been approved for osteoporosis and bone metastasis could now be used to prevent a particularly aggressive form of adenocarcinoma.
Every 30 seconds someone in the world dies of lung cancer. Lung cancer metastases that can develop after a primary tumour are particularly unpredictable and aggressive. Just one in ten people survive for more than five years after being diagnosed with advanced lung cancer. In the 1950s it was proven that chemicals found in tobacco smoke can cause the cells in our body to mutate.
This breakthrough identified one of the leading causes for a wide variety of cancers. It is primarily the cells in the lungs that are affected by smoking as they are directly exposed to these carcinogenic chemicals. Like all cancers, lung cancer is a very complex disease which is triggered by a combination of different environmental and genetic factors. An international team led by IMBA Scientific Director Josef Penninger has now identified a remarkable connection between sex hormones and lung cancer.
Gender medicine puzzle solved
RANK/RANKL are proteins that help determine the body’s bone remodelling and repair function. This bone metabolism mechanism is, in turn, steered by female sex hormones, and plays a role in the normal physiology of the female breast and breast cancer. Until recently, a number of, in many cases, controversial studies proposed that women are more susceptible to lung cancer than men and that lung cancer is more aggressive in women. Until recently, scientists had yet to identify a sex-based trigger for lung cancer.
According to the latest research findings, the RANK/RANKL system plays a significant part in the development of lung cancer, as reported in a new study published in Genes and Development by an international team led by Josef Penninger. The good news: a medicine approved for the treatment of osteoporosis and tested in clinical trials studying hormone-related and congenital breast cancer could prove to be an effective weapon in the fight against lung cancer.
Missing link: RANK/RANKL
One common type of lung cancer, adenocarcinoma, which is caused by a mutation of the KRAS gene, is characterised by its particularly aggressive progression. And it was precisely this carcinoma that researchers looked at in the lungs of mice and people. They found that the previously identified RANK/RANKL signal path is active in the cancer cells and promotes rapid tumour growth.
“For some time, researchers believed that there was a connection between female sex hormones and this aggressive type of lung cancer. And now we have pinpointed the ‘missing link’. In this carcinoma, RANK/RANKL works like a kind of amplifier, particularly in lung cancer stem cells which can be targeted and switched off,” explained Shuan Rao, primary author of the current publication and postdoctoral research fellow at IMBA.
Administering Denosumab, an antibody that has already received regulatory approval, significantly slowed the progression of the disease. With the aggressive KRAS variant of lung cancer, the connection between sex hormones and the development of cancer could open the door to new therapy options. “I am always fascinated by how mysterious and interconnected the body’s signal paths are.
To start with, we were able to find the mechanisms behind osteoporosis with the help of RANK/RANKL, then we succeeded in explaining hormone-related breast cancer and now we have landed at lung cancer,” said Josef Penninger, commenting on the huge potential of his discoveries. Based on earlier data, which showed that lung cancer patients participating in a Denosumab clinical trial lived significantly longer, the blockage of RANKL by the antibody will be tested in a phase 3 study of advanced lung cancer (SPLENDOUR trial: survival improvement in lung cancer induced by denosumab therapy).
“Nobody knew how it worked. Our data now show for the first time that RANK/RANKL has a direct impact on the development of lung cancer – presumably at a very early stage – and that there is a molecular link to gender and sex hormones. As a result, clinical studies should be conducted in much earlier phases of lung cancer development, with a particular focus on the development of cancer in women,” noted Penninger.
Original publication: Rao et al. „RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer", Genes & Development, doi/10.1101/gad.304162.117.
IMBA - Institute of Molecular Biotechnology is one of the leading biomedical research institutes in Europe focusing on cutting-edge functional genomics and stem cell technologies. IMBA is located at the Vienna Biocenter, the vibrant cluster of universities, research institutes and biotech companies in Austria. IMBA is a basic research institute of the Austrian Academy of Sciences, the leading national sponsor of non-university academic research.
About the Vienna BioCenter
The Vienna BioCenter (VBC) is a leading life sciences location in Europe, offering an extraordinary combination of research, education and business on a single campus. About 1,700 employees, more than 1,300 students, 88 research groups, 18 biotech companies, and scientists from more than 69 nations create a highly dynamic environment. This research was part of the VBC PhD Programme.
Mag. Ines Méhu-Blantar | idw - Informationsdienst Wissenschaft
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Materials Sciences
23.03.2018 | Agricultural and Forestry Science
23.03.2018 | Physics and Astronomy