Issue 74, May 2016
bulletInnovation: iManageCancer - A Mobile Platform to Empower Patients & Relatives in Cancer Self-Management
bulletLiquid Biopsies: German-American Firm Develops Blood-Based Lung Cancer Test
bulletInterview with Prof. Dr. Hans-Georg Rammensee - A Global Pioneer in the Field of Personalized Cancer Immunotherapy
bulletBreast Cancer Study Identifies Epigenetic Pattern Associated with Increased Risk for Radiation-Induced Fibrosis
bulletGenetically Engineered Diatom Algae Kill Cancer Cells in Drug Delivery Study
Cancer is among the leading causes of death worldwide. By 2035, the number of cases is expected to increase to 24 million globally, according to the World Cancer Research Fund International. 
In the United States, an estimated 1.685 million new cancer cases will be diagnosed in the year 2016 alone and over 595,000 people are expected to die from the disease. The most common types at present are skin, lung, prostate, breast, colorectal, kidney, bladder, thyroid, and endometrial cancer. National expenditures for cancer care in the U.S. totaled nearly $125 billion in 2010 and could reach $156 billion by 2020. 
To counteract these staggering statistics, medical researchers and professionals are targeting the following areas to improve cancer prevention, diagnosis, and care. Personalized medicine and combination treatments composed of immunotherapies and another form of treatment, like chemo or radiation therapy, are anticipated to be more potent than past care options. In order for this to be successful, however, researchers will first need to continue gaining a deeper understanding of how immune pathways work as well as how drugs could be used effectively to manipulate such pathways to therapeutic advantage. 
Further, improving the collection of high-quality epidemiological and clinical data from patients will play a significant role in enhancing risk assessment and treatment strategies. In the future, we can expect to see more collaborative initiatives on Big Data collection and sharing.
This month's newsletter explores some of the exciting advances that have been made in cancer research in Germany - from the development of liquid biopsies as lung cancer tests to the use of genetically engineered algae as chemotherapy transporters.

Two out of three Americans with invasive cancer survive at least five years after diagnosis, according to the Centers for Disease Control and Prevention (CDC). While significant developments in cancer research have led to more cancer patients being cured, even more are able to live with their ongoing conditions. The disease is now frequently managed as a chronic illness requiring long-term surveillance and, in some cases, maintenance treatment. As a chronic illness, however, an urgent need exists for patients and families to effectively manage their own care.
iManageCancer, a collaborative project under the leadership of the Fraunhofer Institute for Biomedical Engineering (IBMT) in Germany, is meeting this challenge by empowering patients and relatives through a new ICT-based self-management service platform for mobile devices. Supported by eight partners from five European countries, the project seeks to help people better manage cancer throughout all phases of the care continuum in collaboration with their healthcare providers. It is incorporating the latest in gamification from Promotion Software to create intelligent, fun ways to enable those with chronic illnesses to manage their lives in a new, constructive manner.

The platform offers decision-making support to help patients make informed choices about treatment options. It provides users an easy interface to track the health and disease status of therapies as well as the results of clinical interventions and tests. It also has space for users to maintain a health diary on personal clinical observations, such as the side effects of various therapies, and then offers individualized advice on how to manage such unpleasant side effects like pain, nausea, and fatigue.

iManageCancer also serves as an interactive psycho-emotional health assessment instrument for the monitoring of a patient's current psychological and physiological health status, including physical health deterioration and social withdrawal. Based on this assessment, the platform will give personalized tips, for example, coping strategies. Looking ahead, the project's partners hope to incorporate an instrument to analyze data from the anonymized clinical information in order to advance public health research on a whole.

An initial version of the system for clinical testing is expected to be released in the last quarter of this year. For further information, click here. To watch videos about the project, click here.

Source: iManageCancer
Image: eCancer 


Lung cancer is one of the most common and deadliest cancers in the world. China alone has more diagnoses and fatalities than anywhere else globally and that number continues to rise as smoking rates remain alarmingly high and the country's air pollution crisis worsens. By 2020, China is expected to have over 800,000 lung cancer patients a year, according to Chinese state media. 

Currently, there are many biotech efforts focused on finding cancer treatments. However, another strategy for lowering cancer mortality is to improve diagnosis so that people can be treated when their cancers are still at an early stage and manageable.

This is exactly what the German-American cancer molecular diagnostics company, Epigenomics AG, is doing. Based on its expertise in DNA methylation, one of the most studied forms of epigenetic alterations, Epigenomics is developing 'liquid biopsies' or blood-based tests that can quickly diagnose lung cancer based on the presence of certain biomarkers.

The company previously created a product for lung cancer detection called Epi proLung, but that product analyzes bronchial fluid, meaning that patients have to undergo a bronchoscopy. Epigenomic's newest diagnostic only requires a blood analysis. This makes it easier for patients, as the test can be completed as part of a routine visit and there are no dietary restrictions. Furthermore, the test is easy for doctors, as it is simple to explain, which helps drive patient compliance. Finally, the diagnostic is easy for labs because it runs on pre-existing hardware, requiring no further investment in equipment.

Epigenomics is targeting the Chinese market for the initial commercialization of its product. Just two months ago, Epigenomics entered a strategic license and development agreement with BioChain, a leading clinical diagnostics company in cancer and genetic tests in China and the United States. In the first feasibility studies, the DNA methylation panel displayed high sensitivity in detecting lung cancer. BioChain will initiate a clinical trial to validate the lung cancer detection test with the goal of gaining market approval from the China Food and Drug Administration (CFDA). Epigenomics has also received a grant of up to 2.8 million euros from Horizon 2020, the EU's largest research and innovation program, for further development of this test.

Source & Image: Epigenomics AG 

Precision medicine is an emerging new approach to cancer treatment and prevention, which will redefine patient care in the future. Individualized care based on the specific molecular drivers or other biological characteristics of a patient's tumor represents one of the most promising developments in the field of cancer since the emergence of chemotherapies in the late 1940's. 

Prof. Dr. Hans-Georg Rammensee, Director of the Department of Immunology at the Interfaculty Institute for Cell Biology at the University of T�bingen, has been studying the immune system and the different ways to fight cancer for nearly 30 years. He has been devoted to developing effective therapies individualized for each cancer patient.

In 2016, he was awarded the Ernst Jung Prize for Medicine and 300,000 euros for his groundbreaking research on the molecular structure of cell surface peptides. Surface peptides play an important role in the recognition of cells by the immune system. The results of Prof. Dr. Rammensee's research are intended to provide the basis for personalized therapies, an especially promising concept considering that cancer-specific peptides are individual to each patient. The immunobiologist's approach to individualized cancer treatments has already yielded novel clinical applications.

Prof. Dr. Rammensee has worked in the U.S., Switzerland, and Germany, including at the German Cancer Research Center (DKFZ) in Heidelberg. In his interview with GCRI, he discusses how much progress we have made in the war on cancer. He elaborates on some of his current research projects concerning translational immunology and outlines which aspects of his research he would like to focus on next. Finally, he addresses the advantages of personalized immunotherapy. To read the full interview, click here.

To watch a video about Prof. Dr. Rammensee's research career, click here. To read an interview (in German) with the scientist, click here.

Source & Image:

Ever since medical technology has enabled physicians to irradiate tumors more precisely, radiation therapy has become part of the treatment regimen for roughly two-thirds of cancer patients. Radiotherapy is tolerated well in most cases; however, some patients develop side effects. One common, debilitating effect is radiation-induced fibrosis.

Fibrosis is the process of scarring by which healthy tissue is replaced by less elastic connective tissue, which leads to hardening and functional impairments. Radiation-induced fibrosis often occurs as a late effect several months or even years after treatment. However, unlike temporary side effects, such as fatigue or diarrhea, fibrosis is irreversible.

In the case of breast cancer, up to five percent of patients are affected by fibrosis. "If physicians could already tell at the time of diagnosis whether a patient has a particularly high risk for fibrosis, radiation doses could be reduced or other treatment options chosen," Dr. Odilia Popanda from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) said.

To this end, in a recent study on breast cancer, scientists from the DKFZ and the University Medical Centre Mannheim identified an epigenetic pattern that indicates an increased risk for fibrosis. In the future, knowledge of this biomarker could be used before starting radiation therapy.

In the study, the team isolated connective tissue cells from skin biopsies that had been obtained from 75 breast cancer patients prior to radiation therapy. The researchers investigated the DNA of the cells by conducting a genome-wide analysis of the methylation patterns. The investigators found a particularly significant correlation with later developments of radiation-induced fibrosis in the genetic enhancer element of an enzyme called DGKA (diacylglycerol kinase alpha). Patients whose DGKA enhancer exhibited only low numbers of methyl groups later turned out to be highly susceptible to fibrosis. When the researchers treated skin cells in the petri dish with an agent that specifically inhibits the DGKA enzyme, the level of activation of connective tissue cells, which is assumed to be a critical first step in fibrosis, was lower.

Dr. Popanda and her colleagues are pleased to not only have found a biomarker indicating a patient's risk for fibrosis, but also to have potentially discovered a way to prevent this debilitating side effect. DGKA inhibitors have already successfully been used to reduce cancer cell growth and to fight inflammatory processes. In the future, they may also be used to prevent the development of radiation-induced fibrosis.

Source: German Cancer Research Center (DKFZ)
Image: Christoph Bock/Wikimedia Commons 

The ability to selectively kill cancerous cells while leaving healthy cells unaffected is a key goal of anti-cancer therapeutics. The use of nanoporous silica-based materials as drug-delivery vehicles has recently proven to be successful. However, the downside of such materials is that they are expensive and toxic to produce, leading researchers to seek other avenues.

In a joint study by scientists from Germany and South Australia, researchers created synthetic nanoparticles by genetically engineering diatom algae into chemotherapy transporters to selectively kill tumor cells. Diatoms are photosynthesizing microalgae with a siliceous skeleton that are found in nearly every aquatic environment.

By genetically engineering the diatom Thalassiosira pseudonana, chemo drugs can be transported to cancer cells with minimal 'off-target toxicity.' This was accomplished by expressing specific IgG antibodies on the outer surface of the diatom's silica shell. The diatom-chemo packages were thus drawn to the target receptors on B-cell lymphoma and neuroblastoma tumor cells rather than dumping their toxic loads in healthy tissue.

In a mouse xenograft model of neuroblastoma, the nanoengineered algae frustules were shown to successfully regress tumors with fewer side effects from the chemo. These frustules, also described as 'backpacks' for poorly water-soluble chemo drugs, can be cheaply and quickly cultured in mass quantities using basic bioincubators, which require minimal energy consumption.

Results from this study were published in a paper in Nature Communications. The article showcases research from collaborators at the TU Dresden and the Kr�ger Group at the B CUBE Center for Molecular Bioengineering, which is well regarded for its expertise in biomimetic materials. The Kr�ger Group specifically investigates diatoms at a molecular level, i.e. "bioprospecting," for biomimetic nano tools. Bioprospecting is the search for plant and animal species from which medicinal drugs and other commercially valuable compounds can be obtained. B CUBE is financed by the German Federal Ministry of Education and Research (BMBF) as a spin-off of the TU Dresden.

Other partners in this study include the University of Adelaide and the University of South Australia's Future Industries Institute led by Prof. Nico Voelcker, who has long investigated the use of nano-silica porous materials to deliver chemo drugs in cancer.

Image: Delalat et. al 2015, Nature Communications, 6, 8791, doi: 10.1038/ncomms9791

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